Drug Information

Drug (ID: DG00095) and It's Reported Resistant Information
Name
Tamoxifen
Synonyms
Tamoxifen; 10540-29-1; trans-Tamoxifen; Crisafeno; Soltamox; Tamoxifene; Diemon; Tamoxifenum; Tamoxifeno; Tamizam; Istubol; Tamoxen; Citofen; Oncomox; Valodex; Retaxim; Tamoxifene [INN-French]; Tamoxifenum [INN-Latin]; Tamoxifeno [INN-Spanish]; Tamoxifen (Z); Tamoxifen and its salts; Tamoxifen [INN:BAN]; ICI-46474; ICI 47699; TRANS FORM OF TAMOXIFEN; CCRIS 3275; UNII-094ZI81Y45; HSDB 6782; CHEMBL83; EINECS 234-118-0; 1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; Citofen; Nourytam; Novaldex; Tamone; Tamoxifeno;Tamoxifenum; Tomaxithen; Gen-Tamoxifen; Istubal (TN); Nolvadex (TN); Nolvadex-D; Novo-Tamoxifen; Pms-Tamoxifen; Tamoplex (TN); Tamoxifen (INN); Tamoxifen (TN); Trans-Tamoxifen; Valodex (TN); TAMOXIFEN (TAMOXIFEN CITRATE (54965-24-1)); Trans-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine; (Z)-1-(p-Dimethylaminoethoxyphenyl)-1,2-diphenyl-1-butene; (Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine; (Z)-2-(4-(1,2-diphenylbut-1-enyl)phenoxy)-N,N-dimethylethanamine; (Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine (IUPAC); (Z)-2-[4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY]-N,N-DIMETHYLETHANAMINE; (Z)-2-[p-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethylamine; 1-p-beta-Dimethylamino-ethoxyphenyl-trans-1,2-diphenylbut-1-ene; 1-para-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; 2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethylethanamine; 2-{4-[(1Z)-1,2-diphenylbut-1-en-1-yl]phenoxy}-N,N-dimethylethanamine; Tamoxifen (Hormonal therapy); [3H]tamoxifen
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Indication
In total 1 Indication(s)
Breast cancer [ICD-11: 2C60]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
Breast cancer [ICD-11: 2C60]
[2]
Lung cancer [ICD-11: 2C25]
[3]
Ovarian cancer [ICD-11: 2C73]
[3]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Breast cancer [ICD-11: 2C60]
[2]
Target Estrogen receptor (ESR) ESR1_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C26H29NO
IsoSMILES
CC/C(=C(\\C1=CC=CC=C1)/C2=CC=C(C=C2)OCCN(C)C)/C3=CC=CC=C3
InChI
1S/C26H29NO/c1-4-25(21-11-7-5-8-12-21)26(22-13-9-6-10-14-22)23-15-17-24(18-16-23)28-20-19-27(2)3/h5-18H,4,19-20H2,1-3H3/b26-25-
InChIKey
NKANXQFJJICGDU-QPLCGJKRSA-N
PubChem CID
2733526
ChEBI ID
CHEBI:41774
TTD Drug ID
D07KSG
VARIDT ID
DR00193
DrugBank ID
DB00675
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  MRAP: Metabolic Reprogramming via Altered Pathways
  RTDM: Regulation by the Disease Microenvironment
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Breast cancer [ICD-11: 2C60]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: Forkhead box protein O3 (FOXO3) [4]
Metabolic Type Glucose metabolism
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast adenocarcinoma
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.21E-11
Fold-change: 8.33E-01
Z-score: 7.07E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Adrenergic signaling in cardiomyocytes Activation hsa04261
In Vitro Model ZR-75-1 cells Breast Homo sapiens (Human) CVCL_0588
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Here, we report, for the first time, an additional mechanism through which an active FoxO3a can counteract Tam resistance in BCCs. Our data demonstrate how FoxO5a can affect multiple biochemical pathways of BC cell metabolism, spanning from the impairment of glucose breakdown, mitochondrial functionality and NADPH production to the induction of ROS production.
Key Molecule: Forkhead box protein O3 (FOXO3) [4]
Metabolic Type Glucose metabolism
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast adenocarcinoma
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.21E-11
Fold-change: 8.33E-01
Z-score: 7.07E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Adrenergic signaling in cardiomyocytes Activation hsa04261
In Vitro Model T-47D cells N.A. Homo sapiens (Human) CVCL_0553
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Here, we report, for the first time, an additional mechanism through which an active FoxO3a can counteract Tam resistance in BCCs. Our data demonstrate how FoxO4a can affect multiple biochemical pathways of BC cell metabolism, spanning from the impairment of glucose breakdown, mitochondrial functionality and NADPH production to the induction of ROS production.
Key Molecule: Forkhead box protein O3 (FOXO3) [4]
Metabolic Type Glucose metabolism
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast adenocarcinoma
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.21E-11
Fold-change: 8.33E-01
Z-score: 7.07E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Adrenergic signaling in cardiomyocytes Activation hsa04261
In Vitro Model MCF7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Here, we report, for the first time, an additional mechanism through which an active FoxO3a can counteract Tam resistance in BCCs. Our data demonstrate how FoxO3a can affect multiple biochemical pathways of BC cell metabolism, spanning from the impairment of glucose breakdown, mitochondrial functionality and NADPH production to the induction of ROS production.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Metalloproteinase inhibitor 3 (TIMP3) [7]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 4.70E-17
Fold-change: 1.51E+00
Z-score: 9.28E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 WST-8 assay
Mechanism Description Transfection of AS-miR-221 and AS-miR-222 dramatically inhibited expression of miR-221 and miR-222, respectively, in both MCF-7 and MDA-MB-231 cells (P<0.05-0.01). Down-regulation of miR-221/222 significantly increased the expression of TIMP3 compared with controls (P<0.05-0.01). The viability of estrogen receptor (ER)-positive MCF-7 cells transfected with AS-miR-221 or/and AS-miR-222 was significantly reduced by tamoxifen (P<0.05-0.01). Suppression of miRNA-221/222 increases the sensitivity of ER-positive MCF-7 breast cancer cells to tamoxifen. This effect is mediated through upregulation of TIMP3. These findings suggest that upregulation of TIMP3 via inhibition of miRNA-221/222 could be a promising therapeutic approach for breast cancer.
Key Molecule: Estrogen receptor alpha (ESR1) [10]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 5.93E-18
Fold-change: 9.62E-02
Z-score: 8.85E+00
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
BT474 cells Breast Homo sapiens (Human) CVCL_0179
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
Hs-578T cells Breast Homo sapiens (Human) CVCL_0332
MCF10A cells Breast Homo sapiens (Human) CVCL_0598
MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
MDA-MB-361 cells Breast Homo sapiens (Human) CVCL_0620
MDA-MB-435s cells Breast Homo sapiens (Human) CVCL_0622
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-221 and miR-222 are frequently up-regulated in ERalpha-negative breast cancer cell lines and primary tumors. The elevated level of miR-221 and miR-222 is responsible for a subset of ERalpha-negative breast tumors that express ERalpha mRNA. Furthermore, overexpression of miR-221 and miR-222 contributes to tamoxifen resistance through negative regulation of ERalpha, whereas knockdown of miR-221 and/or miR-222 restores ERalpha expression and tamoxifen sensitivity.
Key Molecule: Homeobox protein Hox-B3 (HOXB3) [19]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.06E-04
Fold-change: -2.51E-02
Z-score: -3.73E+00
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR375 inhibits cancer stem cell phenotype and tamoxifen resistance by degrading HOXB3 in human ER-positive breast cancer Overexpression of HOXB3 induced formation of CSC phenotypes, EMT and tamoxifen-resistance as well as enhanced ability of migration and invasion in MCF-7 cells.
Key Molecule: B-cell lymphoma/leukemia 11A (BCL11A) [20]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.20E-14
Fold-change: -1.12E-01
Z-score: -7.79E+00
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation MAPK signaling pathway Inhibition hsa04010
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
MCF-7R cells Breast Homo sapiens (Human) CVCL_Y493
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RIP assay; Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Shikonin reduces tamoxifen resistance of MCF-7R breast cancer cells by inducing uc.57, which downregulates BCL11A to inhibit PI3k/AkT and MAPk signaling pathways.
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Cadherin-1 (CDH1) [9]
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 7.17E-05
Fold-change: 1.76E-01
Z-score: 4.06E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell viability Inhibition hsa05200
Wnt signaling pathway Inhibition hsa04310
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description Knockdown of H19 by siRNA transfection can significantly reduce the expression of N-cadherin, as well as increase E-cadherin and vimentin level, which improved tamoxifen sensitivity in tamoxifen-resistant breast cancer cells.
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: TP53-induced glycolysis and apoptosis regulator (TIGAR) [5]
Metabolic Type Glucose metabolism
Resistant Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast adenocarcinoma
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 5.20E-05
Fold-change: 2.53E-01
Z-score: 4.13E+00
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Apoptosis rate assay
Mechanism Description Mechanistically, TIGAR directly interacts with the antioxidant master regulator NRF2 and facilitates chromatin recruitment of NRF2, H3K4me3 methylase MLL1 and elongating Pol-II to stimulate the expression of both new (NSD2) and established (NQO1/2, PRDX1 and GSTM4) targets of NRF2, independent of its enzymatic activity. Nuclear TIGAR confers cancer cell resistance to chemotherapy and hormonal therapy in vitro and in tumors through effective maintenance of redox homeostasis. In addition, nuclear accumulation of TIGAR is positively associated with NSD2 expression in clinical tumors and strongly correlated with poor survival
Key Molecule: Solute carrier family 16 member 1 (SLC16A1) [6]
Metabolic Type Glucose metabolism
Resistant Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast adenocarcinoma
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 7.57E-07
Fold-change: 3.14E-01
Z-score: 5.09E+00
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF7 cells Breast Homo sapiens (Human) CVCL_0031
MDA-MB-231cells Breast Homo sapiens (Human) CVCL_0062
SK-BR-3 cells Pleural effusion Homo sapiens (Human) CVCL_0033
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description We identified monocarboxylate transporter1 (MCT1) and lactate dehydrogenase B (LDHB) as important mediators of lactate influx and its conversion to pyruvate, respectively. Consistently, AR-C155858 (MCT1 inhibitor) inhibited the proliferation, migration, spheroid formation, and in vivo tumor growth of TAMR-MCF-7 cells.
Key Molecule: Sodium/glucose cotransporter 1 (SGLT1) [49]
Metabolic Type Glucose metabolism
Resistant Disease Estrogen receptor (ER)-positive breast cancer [ICD-11: 2C60.6]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model Estrogen receptor (ER)-positive breast cancer patient Homo Sapiens
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Cell prognosis assay
Mechanism Description Here, we characterized sodium/glucose cotransporter 1 (SGLT1) overexpression drives the highly glycolytic phenotype of tamoxifen-resistant breast cancer cells where enhanced lactic acid secretion promotes M2-like TAM polarization via the hypoxia-inducible factor-1alpha/signal transducer and activator of transcription-4 pathway
Key Molecule: Fatty acid synthase (FASN) [50]
Metabolic Type Lipid metabolism
Resistant Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model HCC patients Homo Sapiens
Experiment for
Molecule Alteration		 Western blot analysis
Mechanism Description Our results revealed that FASN predominates under sensitive conditions, crucially contributing to aerobic respiration. However, its activity diminishes in advanced stages and in tamoxifen-resistant conditions. Conversely, the progressive upregulation of LDHA and the prevalence of anaerobic respiration emerged as metabolic signatures associated with the acquisition of tamoxifen resistance. Subsequently, we delineated the functional roles and metabolic adaptability in response to the inhibition of FASN and LDHA using cellular models representative of tamoxifen-resistant BC.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Metalloproteinase-disintegrin ADAM22-3 (ADAM22) [8]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.97E-01
Fold-change: 3.50E-02
Z-score: 8.49E-01
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
T47D cells Breast Homo sapiens (Human) CVCL_0553
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Decreased miR-449a causes the upregulation of ADAM22, which induces tamoxifen resistance of breast cancer cells.
Key Molecule: Ribonucleoside-diphosphate reductase subunit M2 (RRM2) [11]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.61E-249
Fold-change: 6.99E-01
Z-score: 5.85E+01
Experimental Note Revealed Based on the Cell Line Data
Mechanism Description Increased expression of ribonucleotide reductase subunit M2 (RRM2) was found to be significantly linked to poor survival in all breast cancer patients as well as in ER-positive patients resistant to TAM. Azacytidine treatment in the TAMR cell line results in reduced proliferation and consequently resensitizes cells to TAM treatment. RRM2 is one of the isoforms of the enzyme ribonucleotide reductase, which is involved in the conversion of deoxyribonucleotides from their corresponding ribonucleotides that are required for DNA synthesis. A DNA methyl transferase inhibitor azacytidine has been shown to inhibit the expression of RRM2. Down-regulation of RRM2 by siRNA-mediated approaches significantly reduces TAMR cell growth, invasion and motility. RRM2 inhibition also leads to decreased expression of DNA repair enzymes and elevated expression of pro-apoptotic proteins such as BIM and BAX leading to apoptosis.
Key Molecule: Alpha-enolase (ENO1) [11]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.20E-06
Fold-change: 6.37E-02
Z-score: 4.72E+00
Experimental Note Revealed Based on the Cell Line Data
Mechanism Description Hk2, PFkB3, ENO-1, and PkM-2 are the main enzymes of glycolysis and their expression is upregulated in TAMR cells. Hk2 is also involved in the activation of pro-survival autophagy. ENO-1 plays an important role by inhibiting apoptosis via downregulation of c-Myc. In mitochondria, PDk4 phosphorylation regulate Pyruvate dehydrogenase of PDC. NSD2 activates Hk-2, G6PD, and TIGAR expression and upregulates the PPP pathway. PPP produces NADH and Ribulose 5-Phosphate, a substrate for nucleotide biosynthesis. NADH reduces ROS and inhibits apoptosis. LDHA overexpression helps in aerobic glycolysis and indirectly promotes autophagy. To reduce the concentration of lactate in the cells, MCT expression is increased, which facilitates the efflux of lactate and cell survival.
Key Molecule: Hypoxia-inducible factor 1-alpha (HIF1A) [12]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.47E-15
Fold-change: 4.39E-02
Z-score: 8.20E+00
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
BT474 cells Breast Homo sapiens (Human) CVCL_0179
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Soft agar colony formation assay; Flow cytometry assay
Mechanism Description Long non-coding RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR18a-HIF1alpha feedback regulatory loop. The upregulated UCA1 sponges miR18a, which is a negative regulator of HIF1alpha.
Key Molecule: Transcription factor E2F7 (E2F7) [14]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.07E-215
Fold-change: 2.45E-01
Z-score: 3.81E+01
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
BT474 cells Breast Homo sapiens (Human) CVCL_0179
Hs-578T cells Breast Homo sapiens (Human) CVCL_0332
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Both miR-26a knockdown and E2F7 overexpression conferred resistance to TAM in MCF-7 cells and there is an inverse correlation between miR-26a and E2F7 expression.
Key Molecule: Mucin-1 (MUC1) [11]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 1.85E-53
Fold-change: 2.32E-01
Z-score: 1.73E+01
Experimental Note Revealed Based on the Cell Line Data
Mechanism Description MUC1, an oncoprotein, upregulates the expression of various enzymes involved in cholesterol metabolism. The overexpression of MUC1 has been found to be correlated with TAM resistance and poor survival. Cholesteryl esters of oleic and stearic acids are responsible for the proliferation and invasiveness of tumors. MUC1 upregulates the expression of the ACAT enzyme, therefore inhibition of cancer cell growth by TAM is minimized leading to resistance against it.
Key Molecule: Pyruvate kinase M2 (PKM) [11]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.62E-40
Fold-change: 1.53E-01
Z-score: 1.50E+01
Experimental Note Revealed Based on the Cell Line Data
Mechanism Description Hk2, PFkB3, ENO-1, and PkM-2 are the main enzymes of glycolysis and their expression is upregulated in TAMR cells. Hk2 is also involved in the activation of pro-survival autophagy. ENO-1 plays an important role by inhibiting apoptosis via downregulation of c-Myc. In mitochondria, PDk4 phosphorylation regulate Pyruvate dehydrogenase of PDC. NSD2 activates Hk-2, G6PD, and TIGAR expression and upregulates the PPP pathway. PPP produces NADH and Ribulose 5-Phosphate, a substrate for nucleotide biosynthesis. NADH reduces ROS and inhibits apoptosis. LDHA overexpression helps in aerobic glycolysis and indirectly promotes autophagy. To reduce the concentration of lactate in the cells, MCT expression is increased, which facilitates the efflux of lactate and cell survival.
Key Molecule: Cyclic AMP-responsive element-binding protein 1 (CREB1) [15]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 3.55E-02
Fold-change: 1.23E-02
Z-score: 2.11E+00
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
BT549 cells Breast Homo sapiens (Human) CVCL_1092
MCF10A cells Breast Homo sapiens (Human) CVCL_0598
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Annexin V-FITC (fluorescein isothiocyanate)/PI analysis
Mechanism Description Down-regulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression. Overexpression of NR5A2 and CREB1 reverses reduction of cell viability and induction of apoptosis by miR27b-3p mimics, and depletion of NR5A2 and CREB1 reverses induction of cell viability and reduction of apoptosis by miR509-5p inhibitors in tamoxifen-treated cells.
Key Molecule: Histone-lysine N-methyltransferase NSD2 (NSD2) [16]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 1.57E-54
Fold-change: 1.07E-01
Z-score: 1.75E+01
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
293T cells Breast Homo sapiens (Human) CVCL_0063
In Vivo Model BALB/c nu/nu athymic mice xenografts model Mus musculus
Experiment for
Drug Resistance		 Cell death detection ELISA kit assay
Mechanism Description NSD2 overexpression is significantly associated with high risk of relapse and poor survival in tamoxifen-treated ER-positive breast cancer patients. NSD2 drives tamoxifen therapy resistance through coordinated stimulation of key glucose metabolism enzymes and enhancement of the PPP.
Key Molecule: Solute carrier family 2 member 1 (SLC2A1) [11]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 1.10E-51
Fold-change: 1.07E-01
Z-score: 1.63E+01
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Immunohistochemical assay
Mechanism Description Overexpression of GLUT1 has been reported in aggressive and malignant breast cancer and has been correlated with the poor prognosis. Increased expression of GLUT1 in the TAMR cells compared to the TAM-sensitive cells. knockdown of GLUT1 in TAMR MCF-7 cells resulted in increased expression of p62 protein and decreased levels of LC3B-II, leading to autophagy and cells becoming sensitive to TAM.
Key Molecule: Retinoblastoma-associated protein (RB1) [17]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 9.73E-02
Fold-change: -1.02E-02
Z-score: -1.66E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
BT474 cells Breast Homo sapiens (Human) CVCL_0179
MCF7/TAMR cells Breast Homo sapiens (Human) CVCL_EG55
CAMA-1 cells Breast Homo sapiens (Human) CVCL_1115
HEK293 FT cells Kidney Homo sapiens (Human) CVCL_6911
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description Tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDkN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen. miRNA-519a increases viability and S-phase population of the cell cycle, but does not affect EMT or invasion. miRNA-519a-expressing cells evade tamoxifen-induced apoptosis.
Key Molecule: Tumor protein p73 (TP73) [18]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 6.09E-04
Fold-change: -1.83E-02
Z-score: -3.45E+00
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Western blot analysis; RIP assay; Luciferase reporter assay
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description microRNA 663b mediates TAM resistance in breast cancer by downrerulating TP73 expression.
Key Molecule: Histone deacetylase 4 (HDAC4) [21]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 1.48E-37
Fold-change: -1.85E-01
Z-score: -1.45E+01
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
T47D cells Breast Homo sapiens (Human) CVCL_0553
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Transwell assay
Mechanism Description Over-expression of miR-10b in ER-positive MCF-7 and T47D cells led to increased resistance to tamoxifen and an attenuation of tamoxifen-mediated inhibition of migration, whereas down-regulation of miR-10b in MCF7TR cells resulted in increased sensitivity to tamoxifen. Luciferase assays identified HDAC4 as a direct target of miR-10b. In MCF7TR cells, we observed down-regulation of HDAC4 by miR-10b. HDAC4-specific siRNA-mediated inactivation of HDAC4 in MCF-7 cells led to acquisition of tamoxifen resistance, and, moreover, reduction of HDAC4 in MCF7TR cells by HDAC4-specific siRNA transfection resulted in further enhancement of tamoxifen-resistance.
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: High mobility group protein B3 (HMGB3) [13]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 4.35E-212
Fold-change: 3.28E-01
Z-score: 4.32E+01
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Dual luciferase; Western blot analysis
Experiment for
Drug Resistance		 Transwell assay; Promega assay
Mechanism Description miR-27b is epigenetically downregulated in tamoxifen resistant breast cancer cells due to promoter methylation and regulates tamoxifen sensitivity by targeting HMGB3.
Key Molecule: Protein LYRIC (MTDH) [3]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Breast cancer [ICD-11: 2C60]
The Specified Disease Breast cancer
The Studied Tissue Breast tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 2.31E-53
Fold-change: 1.10E-01
Z-score: 1.82E+01
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Activation hsa04670
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Cell titer glo assay
Mechanism Description Overexpression of MTDH increased mesenchymal markers while downregulating E-cadherin expression, associated with poor prognosis and increased risk of metastasis in breast cancer. Tamoxifen-sensitive cells expressing miRNA-375 at high levels directly represses MTDH expression, and that this regulation confers the cells with a tamoxifen sensitive and epithelial phenotype.
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Estrogen receptor alpha (ESR1) [23], [24], [25]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.Y537S
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.60  Å
PDB: 2IOG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.50  Å
PDB: 5DXE
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.7
TM score: 0.91757
Amino acid change:
Y537S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
D
-
P
-
M
-
I
-
K
300
|
-
R
-
S
-
K
-
K
-
N
-
S
-
L
-
A
-
L
S
S
310
|
L
L
T
T
A
A
D
D
Q
Q
M
M
V
V
S
S
A
A
L
L
320
|
L
L
D
D
A
A
E
E
P
P
P
P
I
I
L
L
Y
Y
S
S
330
|
E
E
Y
Y
D
D
P
P
T
T
R
R
P
P
F
F
S
S
E
E
340
|
A
A
S
S
M
M
M
M
G
G
L
L
L
L
T
T
N
N
L
L
350
|
A
A
D
D
R
R
E
E
L
L
V
V
H
H
M
M
I
I
N
N
360
|
W
W
A
A
K
K
R
R
V
V
P
P
G
G
F
F
V
V
D
D
370
|
L
L
T
T
L
L
H
H
D
D
Q
Q
V
V
H
H
L
L
L
L
380
|
E
E
C
-
A
A
W
W
L
L
E
E
I
I
L
L
M
M
I
I
390
|
G
G
L
L
V
V
W
W
R
R
S
S
M
M
E
E
H
H
P
P
400
|
G
G
K
K
L
L
L
L
F
F
A
A
P
P
N
N
L
L
L
L
410
|
L
L
D
D
R
R
N
N
Q
Q
G
G
K
K
C
-
V
V
E
E
420
|
G
G
M
M
V
V
E
E
I
I
F
F
D
D
M
M
L
L
L
L
430
|
A
A
T
T
S
S
S
S
R
R
F
F
R
R
M
M
M
M
N
N
440
|
L
L
Q
Q
G
G
E
E
E
E
F
F
V
V
C
C
L
L
K
K
450
|
S
S
I
I
I
I
L
L
L
L
N
N
S
S
G
G
V
V
Y
Y
460
|
T
T
F
F
L
L
S
S
S
S
T
T
L
L
K
K
S
S
L
L
470
|
E
E
E
E
K
K
D
D
H
H
I
I
H
H
R
R
V
V
L
L
480
|
D
D
K
K
I
I
T
T
D
D
T
T
L
L
I
I
H
H
L
L
490
|
M
M
A
A
K
K
A
A
G
G
L
L
T
T
L
L
Q
Q
Q
Q
500
|
Q
Q
H
H
Q
Q
R
R
L
L
A
A
Q
Q
L
L
L
L
L
L
510
|
I
I
L
L
S
S
H
H
I
I
R
R
H
H
M
M
S
S
N
N
520
|
K
K
G
G
M
M
E
E
H
H
L
L
Y
Y
S
S
M
M
K
K
530
|
C
-
K
K
N
N
V
V
V
V
P
P
L
L
Y
S
D
D
L
L
540
|
L
L
L
L
E
E
M
M
L
L
D
D
A
A
H
H
R
R
L
L
550
|
H
H
A
A
P
P
T
T
S
S
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation PI3K signaling pathway Activation hsa04151
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Whole-exome sequencing assay; SNP Array profiling assay
Experiment for
Drug Resistance		 Tumor biopsy assay
Mechanism Description Mutations in ESR1 were detected in 4% of cancers and clustered in the ligand-binding domain. These included p.Tyr537(Cys/Asn/Ser) mutations (three patients) that have been shown to cause constitutive activation and resistance to tamoxifen therapy in breast cancer.
Key Molecule: Estrogen receptor alpha (ESR1) [24]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.D538G
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.60  Å
PDB: 2IOG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.90  Å
PDB: 4PXM
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.86
TM score: 0.90649
Amino acid change:
D538G
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
V
-
D
-
L
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G
-
T
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E
290
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-
N
-
L
-
Y
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F
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-
N
-
A
-
M
-
K
300
|
-
R
-
S
-
K
-
K
-
N
-
S
-
L
-
A
-
L
S
S
310
|
L
L
T
T
A
A
D
D
Q
Q
M
M
V
V
S
S
A
A
L
L
320
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L
L
D
D
A
A
E
E
P
P
P
P
I
I
L
L
Y
Y
S
S
330
|
E
E
Y
Y
D
D
P
P
T
T
R
R
P
P
F
F
S
S
E
E
340
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A
A
S
S
M
M
M
M
G
G
L
L
L
L
T
T
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N
L
L
350
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A
A
D
D
R
R
E
E
L
L
V
V
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H
M
M
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N
N
360
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W
W
A
A
K
K
R
R
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V
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P
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G
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F
V
V
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D
370
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L
L
T
T
L
L
H
H
D
D
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V
H
H
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L
L
380
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E
E
C
C
A
A
W
W
L
L
E
E
I
I
L
L
M
M
I
I
390
|
G
G
L
L
V
V
W
W
R
R
S
S
M
M
E
E
H
H
P
P
400
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G
G
K
K
L
L
L
L
F
F
A
A
P
P
N
N
L
L
L
L
410
|
L
L
D
D
R
R
N
N
Q
Q
G
G
K
K
C
C
V
V
E
E
420
|
G
G
M
M
V
V
E
E
I
I
F
F
D
D
M
M
L
L
L
L
430
|
A
A
T
T
S
S
S
S
R
R
F
F
R
R
M
M
M
M
N
N
440
|
L
L
Q
Q
G
G
E
E
E
E
F
F
V
V
C
C
L
L
K
K
450
|
S
S
I
I
I
I
L
L
L
L
N
N
S
S
G
G
V
V
Y
Y
460
|
T
T
F
F
L
L
S
S
S
S
T
T
L
L
K
K
S
S
L
L
470
|
E
E
E
E
K
K
D
D
H
H
I
I
H
H
R
R
V
V
L
L
480
|
D
D
K
K
I
I
T
T
D
D
T
T
L
L
I
I
H
H
L
L
490
|
M
M
A
A
K
K
A
A
G
G
L
L
T
T
L
L
Q
Q
Q
Q
500
|
Q
Q
H
H
Q
Q
R
R
L
L
A
A
Q
Q
L
L
L
L
L
L
510
|
I
I
L
L
S
S
H
H
I
I
R
R
H
H
M
M
S
S
N
N
520
|
K
K
G
G
M
M
E
E
H
H
L
L
Y
Y
S
S
M
M
K
K
530
|
C
C
K
K
N
N
V
V
V
V
P
P
L
L
Y
Y
D
G
L
L
540
|
L
L
L
L
E
E
M
M
L
L
D
D
A
A
H
H
R
R
L
L
550
|
H
H
A
A
P
P
T
T
S
S
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Mechanism Description In our analysis of frequently mutated oncogenes and tumor suppressors, ESR1 mutations stood out as a common and plausible event that could contribute to resistance. We found that the mutations in both Tyr537 and Asp538 strongly promoted ER signaling in absence of ligand. This was observed biochemically as increased phosphorylation on S118, increased association with AIB1, and diminished sensitivity to HSP90 inhibitors. Functionally, the mutations in vitro promoted the expression of classical ER target genes in the absence of hormone.
Key Molecule: Estrogen receptor alpha (ESR1) [23], [25], [26]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.D538G
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.60  Å
PDB: 2IOG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.90  Å
PDB: 4PXM
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.86
TM score: 0.90649
Amino acid change:
D538G
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
V
-
D
-
L
-
G
-
T
-
E
290
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-
N
-
L
-
Y
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F
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S
-
N
-
A
-
M
-
K
300
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R
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-
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-
K
-
N
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S
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L
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A
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L
S
S
310
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L
L
T
T
A
A
D
D
Q
Q
M
M
V
V
S
S
A
A
L
L
320
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L
L
D
D
A
A
E
E
P
P
P
P
I
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L
L
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Y
S
S
330
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E
E
Y
Y
D
D
P
P
T
T
R
R
P
P
F
F
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S
E
E
340
|
A
A
S
S
M
M
M
M
G
G
L
L
L
L
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T
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N
L
L
350
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A
A
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D
R
R
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E
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H
M
M
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I
N
N
360
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W
W
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A
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K
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R
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G
G
F
F
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D
370
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L
L
T
T
L
L
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H
D
D
Q
Q
V
V
H
H
L
L
L
L
380
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E
E
C
C
A
A
W
W
L
L
E
E
I
I
L
L
M
M
I
I
390
|
G
G
L
L
V
V
W
W
R
R
S
S
M
M
E
E
H
H
P
P
400
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G
G
K
K
L
L
L
L
F
F
A
A
P
P
N
N
L
L
L
L
410
|
L
L
D
D
R
R
N
N
Q
Q
G
G
K
K
C
C
V
V
E
E
420
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G
G
M
M
V
V
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E
I
I
F
F
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D
M
M
L
L
L
L
430
|
A
A
T
T
S
S
S
S
R
R
F
F
R
R
M
M
M
M
N
N
440
|
L
L
Q
Q
G
G
E
E
E
E
F
F
V
V
C
C
L
L
K
K
450
|
S
S
I
I
I
I
L
L
L
L
N
N
S
S
G
G
V
V
Y
Y
460
|
T
T
F
F
L
L
S
S
S
S
T
T
L
L
K
K
S
S
L
L
470
|
E
E
E
E
K
K
D
D
H
H
I
I
H
H
R
R
V
V
L
L
480
|
D
D
K
K
I
I
T
T
D
D
T
T
L
L
I
I
H
H
L
L
490
|
M
M
A
A
K
K
A
A
G
G
L
L
T
T
L
L
Q
Q
Q
Q
500
|
Q
Q
H
H
Q
Q
R
R
L
L
A
A
Q
Q
L
L
L
L
L
L
510
|
I
I
L
L
S
S
H
H
I
I
R
R
H
H
M
M
S
S
N
N
520
|
K
K
G
G
M
M
E
E
H
H
L
L
Y
Y
S
S
M
M
K
K
530
|
C
C
K
K
N
N
V
V
V
V
P
P
L
L
Y
Y
D
G
L
L
540
|
L
L
L
L
E
E
M
M
L
L
D
D
A
A
H
H
R
R
L
L
550
|
H
H
A
A
P
P
T
T
S
S
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Circulating cell-free DNA assay; Liquid biopsy assay; Droplet digital PCR assay; Next generation assay
Experiment for
Drug Resistance		 Progression-free survival assay; Overall survival assay
Mechanism Description Recent studies have also highlighted the utility of ex vivo culturing of CTCs as a method of individualized drug susceptibility testing. Using this method, the authors found that CTCs have various mutations (including the p.D538G and p.Y537S ESR1 mutations), and showed that low-dose administration of the HSP90 inhibitor STA9090 alone or in combination with raloxifene and fulvestrant has growth-inhibitory effects.
Key Molecule: Estrogen receptor alpha (ESR1) [27]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.L536_D538>P
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Next-generation sequencing assay
Experiment for
Drug Resistance		 Overall survival assay
Mechanism Description All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.
Key Molecule: Estrogen receptor alpha (ESR1) [24], [28], [29]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.Y537N
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation PI3K signaling pathway Activation hsa04151
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Whole-exome sequencing assay; SNP Array profiling assay
Experiment for
Drug Resistance		 Tumor biopsy assay
Mechanism Description Mutations in ESR1 were detected in 4% of cancers and clustered in the ligand-binding domain. These included p.Tyr537(Cys/Asn/Ser) mutations (three patients) that have been shown to cause constitutive activation and resistance to tamoxifen therapy in breast cancer.
Key Molecule: Estrogen receptor alpha (ESR1) [24], [29], [30]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.Y537C
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation PI3K signaling pathway Activation hsa04151
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Whole-exome sequencing assay; SNP Array profiling assay
Experiment for
Drug Resistance		 Tumor biopsy assay
Mechanism Description Mutations in ESR1 were detected in 4% of cancers and clustered in the ligand-binding domain. These included p.Tyr537(Cys/Asn/Ser) mutations (three patients) that have been shown to cause constitutive activation and resistance to tamoxifen therapy in breast cancer.
Key Molecule: Estrogen receptor alpha (ESR1) [23]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Missense mutation
p.L536Q
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration		 Whole-genome sequencing assay
Mechanism Description Whole-exome and transcriptome analysis showed that six cases harbored mutations of ESR1 affecting its ligand-binding domain (LBD), all of whom had been treated with anti-estrogens and estrogen deprivation therapies.
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa_circ_0025202 [1]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay; Colony formation assay
Mechanism Description Hsa_circ_0025202 suppressed BC progression and sensitized cells to TAM via sponging miR-182-5p, thereby attenuating its oncogenic effect.
Key Molecule: hsa-miR-182-5p [1]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay; Colony formation assay
Mechanism Description Hsa_circ_0025202 suppressed BC progression and sensitized cells to TAM via sponging miR-182-5p, thereby attenuating its oncogenic effect.
Key Molecule: ADAMTS9 antisense RNA 2 (ADAMTS9-AS2) [31]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description Downregulated LncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p.
Key Molecule: hsa-miR-130a-5p [31]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description Downregulated LncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p.
Key Molecule: Urothelial cancer associated 1 (UCA1) [12], [32], [33]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
mTOR signaling pathway Activation hsa04150
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
BT474 cells Breast Homo sapiens (Human) CVCL_0179
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Soft agar colony formation assay; Flow cytometry assay
Mechanism Description Long non-coding RNA UCA1 enhances tamoxifen resistance in ER positive breast cancer cells through a miR18a-HIF1alpha feedback regulatory loop.
Key Molecule: Long non-protein coding RNA, regulator of reprogramming (LINC-ROR) [34]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation MAPK/ERK signaling pathway Activation hsa04011
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
RoR kO cells Breast Homo sapiens (Human) N.A.
GRNA control cells Breast Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Linc-RoR causes the upregulation of phosphorylated MAPk/ERk pathway which in turn activates ER signaling. Linc-RoR promotes estrogen-independent growth and activation of MAPk/ERk pathway of breast cancer cells by regulating the ERk-specific phosphatase DUSP7.
Key Molecule: hsa-mir-18a [33]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
BT474 cells Breast Homo sapiens (Human) CVCL_0179
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 qRT-PCR; Dual luciferase assay
Experiment for
Drug Resistance		 CCK8 assay; Soft agar assay; Flow cytometric analysis
Mechanism Description Long non-coding RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR18a-HIF1alpha feedback regulatory loop. The upregulated UCA1 sponges miR18a, which is a negative regulator of HIF1alpha.
Key Molecule: hsa-miR-335-3p [35]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ER-alpha signaling pathway Inhibition hsa04915
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Crystal Violet Assay
Mechanism Description microRNA-335-5p and -3p synergize to inhibit estrogen receptor alpha expression and promote tamoxifen resistance. MiRNA duplex repressed genes involved in the ERalpha signaling pathway, and enhanced resistance of MCF-7 cells to the growth inhibitory effects of tamoxifen.
Key Molecule: hsa-miR-335-5p [35]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ER-alpha signaling pathway Inhibition hsa04915
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Crystal Violet Assay
Mechanism Description microRNA-335-5p and -3p synergize to inhibit estrogen receptor alpha expression and promote tamoxifen resistance. MiRNA duplex repressed genes involved in the ERalpha signaling pathway, and enhanced resistance of MCF-7 cells to the growth inhibitory effects of tamoxifen.
Key Molecule: hsa-miR-27b-3p [15]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
BT549 cells Breast Homo sapiens (Human) CVCL_1092
MCF10A cells Breast Homo sapiens (Human) CVCL_0598
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay; Annexin V-FITC (fluorescein isothiocyanate)/PI analysis
Mechanism Description Down-regulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression. Overexpression of NR5A2 and CREB1 reverses reduction of cell viability and induction of apoptosis by miR27b-3p mimics, and depletion of NR5A2 and CREB1 reverses induction of cell viability and reduction of apoptosis by miR509-5p inhibitors in tamoxifen-treated cells.
Key Molecule: Urothelial cancer associated 1 (UCA1) [36]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
PI3K/AKT signaling pathway Activation hsa04151
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
T47D cells Breast Homo sapiens (Human) CVCL_0553
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 RT-PCR,RT-qPCR
Experiment for
Drug Resistance		 WST-1 assay; Flow cytometry assay
Mechanism Description UCA1 was physically associated with the enhancer of zeste homolog 2 (EZH2), which suppressed the expression of p21 through histone methylation (H3k27me3) on the p21 promoter and the induced overexpression of UCA1 decreased the drug sensitivity of tamoxifen.
Key Molecule: hsa-miR-449a [8]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
T47D cells Breast Homo sapiens (Human) CVCL_0553
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Decreased miR-449a causes the upregulation of ADAM22, which induces tamoxifen resistance of breast cancer cells.
Key Molecule: hsa-mir-26a [14]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
BT474 cells Breast Homo sapiens (Human) CVCL_0179
Hs-578T cells Breast Homo sapiens (Human) CVCL_0332
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Both miR-26a knockdown and E2F7 overexpression conferred resistance to TAM in MCF-7 cells and there is an inverse correlation between miR-26a and E2F7 expression.
Key Molecule: hsa-miR-663b [18]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description microRNA 663b mediates TAM resistance in breast cancer by downrerulating TP73 expression.
Key Molecule: hsa-mir-155 [37]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
SOCS6/STAT3 signaling pathway Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Inhibition of miR-155 sensitizes breast cancer cells to tamoxifen and SOCS6 sensitizes the cells to tamoxifen.
Key Molecule: HOX transcript antisense RNA (HOTAIR) [38]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
ER signaling pathway Activation hsa04915
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
T47D cells Breast Homo sapiens (Human) CVCL_0553
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 WST1 assay
Mechanism Description HOTAIR overexpression increases breast cancer cell proliferation, whereas its depletion significantly impairs cell survival and abolishes tamoxifen-resistant cell growth. The LncRNA HOTAIR is directly repressed by ER and its up-regulation promotes ligand-independent ER activities and contributes to tamoxifen resistance.
Key Molecule: hsa-mir-10b [21]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
T47D cells Breast Homo sapiens (Human) CVCL_0553
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay; Transwell assay
Mechanism Description Over-expression of miR-10b in ER-positive MCF-7 and T47D cells led to increased resistance to tamoxifen and an attenuation of tamoxifen-mediated inhibition of migration, whereas down-regulation of miR-10b in MCF7TR cells resulted in increased sensitivity to tamoxifen. Luciferase assays identified HDAC4 as a direct target of miR-10b. In MCF7TR cells, we observed down-regulation of HDAC4 by miR-10b. HDAC4-specific siRNA-mediated inactivation of HDAC4 in MCF-7 cells led to acquisition of tamoxifen resistance, and, moreover, reduction of HDAC4 in MCF7TR cells by HDAC4-specific siRNA transfection resulted in further enhancement of tamoxifen-resistance.
Key Molecule: hsa-mir-519a [17]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
BT474 cells Breast Homo sapiens (Human) CVCL_0179
MCF7/TAMR cells Breast Homo sapiens (Human) CVCL_EG55
CAMA-1 cells Breast Homo sapiens (Human) CVCL_1115
HEK293 FT cells Kidney Homo sapiens (Human) CVCL_6911
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Promega assay
Mechanism Description Tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDkN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen. miRNA-519a increases viability and S-phase population of the cell cycle, but does not affect EMT or invasion. miRNA-519a-expressing cells evade tamoxifen-induced apoptosis.
Key Molecule: hsa-let-7b [39]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ER-alpha 36 mediated nongenomic estrogen signaling pathway Activation hsa04915
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
MDA-MB-436 cells Breast Homo sapiens (Human) CVCL_0623
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
184A1 cells Breast Homo sapiens (Human) CVCL_3040
HB3396 cells Breast Homo sapiens (Human) N.A.
MEGM cells Breast Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Breast cancer patients with tumors highly expressing ER-alpha36 benefit less from tamoxifen treatment. Both mRNA and protein expression of ER-alpha36 were inhibited by let-7 mimics and enhanced by let-7 inhibitors. Our results suggested a novel regulatory mechanism of let-7 miRNAs on ER-alpha36 mediated nongenomic estrogen signal pathways and Tam resistance.
Key Molecule: hsa-let-7i [39]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ER-alpha 36 mediated nongenomic estrogen signaling pathway Activation hsa04915
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
SkBR3 cells Breast Homo sapiens (Human) CVCL_0033
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
MDA-MB-436 cells Breast Homo sapiens (Human) CVCL_0623
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
184A1 cells Breast Homo sapiens (Human) CVCL_3040
HB3396 cells Breast Homo sapiens (Human) N.A.
MEGM cells Breast Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Breast cancer patients with tumors highly expressing ER-alpha36 benefit less from tamoxifen treatment. Both mRNA and protein expression of ER-alpha36 were inhibited by let-7 mimics and enhanced by let-7 inhibitors. Our results suggested a novel regulatory mechanism of let-7 miRNAs on ER-alpha36 mediated nongenomic estrogen signal pathways and Tam resistance.
Key Molecule: hsa-mir-342 [40]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR; Northern blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-342 regulates expression of genes involved in tamoxifen mediated tumor cell apoptosis and cell cycle progression.
Key Molecule: Breast cancer anti-estrogen resistance 4 (BCAR4) [41]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation ERBB2/ERBB3 signaling pathway Activation hsa04012
In Vitro Model ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Response evaluation criteria in solid tumors assay
Mechanism Description In BCAR4-expressing cells, phosphorylation of v-erb-b2 erythroblastic leukaemia viral oncogene homolog (ERBB) 2, ERBB3, and their downstream mediators extracellular signal-regulated kinase 1/2 and v-akt murine thymoma viral oncogene homolog (AkT) 1/2, was increased. Selective knockdown of ERBB2 or ERBB3 inhibited proliferation, confirming their role in BCAR4-induced tamoxifen resistance.
Key Molecule: hsa-mir-221 [2]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Ectopic expression of miR-221/222 rendered the parental MCF-7 cells resistant to tamoxifen. The protein level of the cell cycle inhibitor p27kip1, a known target of miR-221/222, was reduced by 50% in OHTR cells and by 28-50% in miR-221/222-overexpressing MCF-7 cells. Furthermore, overexpression of p27kip1 in the resistant OHTR cells caused enhanced cell death when exposed to tamoxifen.
Key Molecule: hsa-mir-222 [2]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Ectopic expression of miR-221/222 rendered the parental MCF-7 cells resistant to tamoxifen. The protein level of the cell cycle inhibitor p27kip1, a known target of miR-221/222, was reduced by 50% in OHTR cells and by 28-50% in miR-221/222-overexpressing MCF-7 cells. Furthermore, overexpression of p27kip1 in the resistant OHTR cells caused enhanced cell death when exposed to tamoxifen.
Key Molecule: Arylamine N-acetyltransferase 1 (NAT1) [42]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Molecule Alteration Epigenetic modification
Methylation aberrance
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 Bisulfite genomic sequencing assay; Methylation-specific PCR assay
Mechanism Description Taken together, the higher methylation rate of the NAT1 gene is related to tamoxifen resistance, and this fact supports the hypothesis that hypermethylation of the NAT1 gene might affect the initiation of tamoxifen resistance.
Key Molecule: Nuclear receptor subfamily 6 group A member 1 (NR6A1) [43]
Resistant Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Epigenetic modification
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF7 cells Breast Homo sapiens (Human) CVCL_0031
MDA-MB-231cells Breast Homo sapiens (Human) CVCL_0062
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay; Immunoblotting assay assay
Mechanism Description Resistance to tamoxifen and rapamycin is associated with the suppression of DNMT3A.Suppresses ERalpha activity, induces partial resistance to rapamycin and tamoxifen, and slightly decreases DNMT3A expression, indicating a functional interplay between NR6A1 and DNMT3A signaling. The development of cross-resistance in breast cancer cells to hormonal and targeted therapies involves a shift in cell signaling to alternative AKT pathways, marked by a localized suppression of the NR6A1/DNMT3A axis and associated DNA methylation changes.
Key Molecule: hsa-miR-203a [2]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 MiRNA microarray profiling, TaqMan Reverse Transcription (RT)-PCR for miRNA Quantification
Experiment for
Drug Resistance		 Cell Proliferation Assay, Apoptosis Assay
Mechanism Description miRNA microarray analysis of MCF-7 cell lines that are either sensitive (parental) or resistant (4-hydroxytamoxifen-resistant (OHTR)) to tamoxifen showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down-regulation (>50%) of seven miRNAs in OHTRcells compared with parental MCF-7 cells.
Key Molecule: hsa-miR-24-1 [2]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 MiRNA microarray profiling, TaqMan Reverse Transcription (RT)-PCR for miRNA Quantification
Experiment for
Drug Resistance		 Cell Proliferation Assay, Apoptosis Assay
Mechanism Description miRNA microarray analysis of MCF-7 cell lines that are either sensitive (parental) or resistant (4-hydroxytamoxifen-resistant (OHTR)) to tamoxifen showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down-regulation (>50%) of seven miRNAs in OHTRcells compared with parental MCF-7 cells.
Key Molecule: hsa-miR-181a-1 [2]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 MiRNA microarray profiling, TaqMan Reverse Transcription (RT)-PCR for miRNA Quantification
Experiment for
Drug Resistance		 Cell Proliferation Assay, Apoptosis Assay
Mechanism Description miRNA microarray analysis of MCF-7 cell lines that are either sensitive (parental) or resistant (4-hydroxytamoxifen-resistant (OHTR)) to tamoxifen showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down-regulation (>50%) of seven miRNAs in OHTRcells compared with parental MCF-7 cells.
Key Molecule: hsa-miR-32 [2]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 MiRNA microarray profiling, TaqMan Reverse Transcription (RT)-PCR for miRNA Quantification
Experiment for
Drug Resistance		 Cell Proliferation Assay, Apoptosis Assay
Mechanism Description miRNA microarray analysis of MCF-7 cell lines that are either sensitive (parental) or resistant (4-hydroxytamoxifen-resistant (OHTR)) to tamoxifen showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down-regulation (>50%) of seven miRNAs in OHTRcells compared with parental MCF-7 cells.
Key Molecule: hsa-miR-489 [2]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 MiRNA microarray profiling, TaqMan Reverse Transcription (RT)-PCR for miRNA Quantification
Experiment for
Drug Resistance		 Cell Proliferation Assay, Apoptosis Assay
Mechanism Description miRNA microarray analysis of MCF-7 cell lines that are either sensitive (parental) or resistant (4-hydroxytamoxifen-resistant (OHTR)) to tamoxifen showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down-regulation (>50%) of seven miRNAs in OHTRcells compared with parental MCF-7 cells.
Key Molecule: hsa-miR-128-1 [44]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUM1315 cells Breast Homo sapiens (Human) CVCL_5589
Experiment for
Molecule Alteration		 MiRNA microarray; RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description We focused our work on hsa-miR-128a which was hormone-responsive and selectively up-regulated in the letrozole-resistant cell lines. Human miR-128a was predicted to target the TGFbeta signaling pathway and indeed sensitivity to TGFbeta was compromised in the letrozole-resistant cells, as compared to parental MCF-7aro. Human miR-128a was shown to negatively target TGFbetaRI protein expression by binding to the 3'UTR region of the gene. Inhibition of endogenous miR-128a resulted in re-sensitization of the letrozole-resistant lines to TGFbeta growth inhibitory effects.
Key Molecule: hsa-miR-320a [45]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
T47D cells Breast Homo sapiens (Human) CVCL_0553
Experiment for
Molecule Alteration		 Real-time PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description To investigate the role of miR-320a in the development of resistance to tamoxifen, we established tamoxifen-resistant (TamR) models by continually exposing MCF-7 or T47D breast cancer cells to tamoxifen, and identified microRNA(miRNA)-320a as a down-regulated miRNA in tamoxifen resistant cells. Re-expression of miR-320a was sufficient to sensitize TamR cells to tamoxifen by targeting cAMP-regulated phosphoprotein (ARPP-19) and estrogen-related receptor gamma (ERR) as well as their downstream effectors, c-Myc and Cyclin D1. Furthermore, progesterone (P4) promoted the expression of miR-320a by repressing c-Myc expression, while estrogen (E2) exerted the opposite effect.
Key Molecule: hsa-miR-517c [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-518c [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-518b [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-520b [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-519c [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-515-1 [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-512-1 [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-516a-1 [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-518e [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-518f [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-519e [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-330 [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-519d [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-520h [22]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation PI3K-AKT signalling pathway Regulation N.A.
Cell cycle pathways Regulation N.A.
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell viability assay; Cell cycle assays; Apoptosis assay
Mechanism Description Our findings indicate that tamoxifen-resistant cells express miRNA-519a at high levels, which directly represses the expression of PTEN, RB1, and CDKN1A, central nodes of a dense network, allowing the cells to proliferate, even in the presence of tamoxifen.
Key Molecule: hsa-miR-15a [46]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
In Vivo Model NU/NU immune compromised mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Luciferase reporter assay
Experiment for
Drug Resistance		 Apoptosis assay; Cell proliferation assay
Mechanism Description In addition, HER2 16 expression results in suppression of BCL-2-targeting microRNAs miR-15a and miR-16
Key Molecule: hsa-miR-103a-1 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-196a-1 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-365a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-425 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-450a-1 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-665 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-891a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-549a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-615 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-550a-1 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-510 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-18b [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-423 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-345 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-339 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-331 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-105-1 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-625 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-628 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-7-1 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-744 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-99b [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-17 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-19a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-20a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-96 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-100 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-29b-1 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-106a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-197 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-10a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-34a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-182 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-183 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-200b [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-125b-1 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-141 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-125a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-126 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-149 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-185 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-193a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-200c [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-200a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-361 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-374a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-378a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-151a [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-148b [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-324 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-193b [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-374b [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-939 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-107 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-429 [47]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
LCC2 cells Breast Homo sapiens (Human) CVCL_DP51
LCC9 cells Breast Homo sapiens (Human) CVCL_DP52
Experiment for
Molecule Alteration		 Microarray analyses; qPCR; RT-PCR; Western blot
Mechanism Description Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen (4-OHT) regulated in MCF-7 endocrine- sensitive versus resistant LY2 human breast cancer cells. 97 miRNAs were differentially expressed in MCF-7 versus LY2 cells. Opposite expression of miRs- 10a, 21, 22, 29a, 93, 125b, 181, 200a, 200b, 200c, 205, and 222 was confirmed.
Key Molecule: hsa-miR-92a-3p [48]
Resistant Disease Breast cancer [ICD-11: 2C60.2]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Microarray analysis; qRT-PCR
Mechanism Description The abnormal expression of miR-92a-3p was detected in multiple cancers
Ovarian cancer [ICD-11: 2C73]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Protein LYRIC (MTDH) [3]
Resistant Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Ovarian cancer [ICD-11: 2C73]
The Specified Disease Ovarian cancer
The Studied Tissue Ovarian tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 4.25E-03
Fold-change: 9.64E-02
Z-score: 3.90E+00
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Activation hsa04670
In Vitro Model OVCAR5 cells Ovary Homo sapiens (Human) CVCL_1628
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Cell titer glo assay
Mechanism Description Overexpression of MTDH increased mesenchymal markers while downregulating E-cadherin expression, associated with poor prognosis and increased risk of metastasis in breast cancer. Tamoxifen-sensitive cells expressing miRNA-375 at high levels directly represses MTDH expression, and that this regulation confers the cells with a tamoxifen sensitive and epithelial phenotype.
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Protein LYRIC (MTDH) [3]
Resistant Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Lung cancer [ICD-11: 2C25]
The Specified Disease Lung cancer
The Studied Tissue Lung tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 1.83E-11
Fold-change: 2.75E-02
Z-score: 6.93E+00
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Activation hsa04670
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1703 cells Lung Homo sapiens (Human) CVCL_1490
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Cell titer glo assay
Mechanism Description Overexpression of MTDH increased mesenchymal markers while downregulating E-cadherin expression, associated with poor prognosis and increased risk of metastasis in breast cancer. Tamoxifen-sensitive cells expressing miRNA-375 at high levels directly represses MTDH expression, and that this regulation confers the cells with a tamoxifen sensitive and epithelial phenotype.
Key Molecule: hsa-mir-375 [3]
Resistant Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Activation hsa04670
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
H1703 cells Lung Homo sapiens (Human) CVCL_1490
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Cell titer glo assay
Mechanism Description Overexpression of MTDH increased mesenchymal markers while downregulating E-cadherin expression, associated with poor prognosis and increased risk of metastasis in breast cancer. Tamoxifen-sensitive cells expressing miRNA-375 at high levels directly represses MTDH expression, and that this regulation confers the cells with a tamoxifen sensitive and epithelial phenotype.
References
Ref 1 circRNA_0025202 Regulates Tamoxifen Sensitivity and Tumor Progression via Regulating the miR-182-5p/FOXO3a Axis in Breast Cancer. Mol Ther. 2019 Sep 4;27(9):1638-1652. doi: 10.1016/j.ymthe.2019.05.011. Epub 2019 May 17.
Ref 2 MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem. 2008 Oct 31;283(44):29897-903. doi: 10.1074/jbc.M804612200. Epub 2008 Aug 15.
Ref 3 Re-expression of microRNA-375 reverses both tamoxifen resistance and accompanying EMT-like properties in breast cancer. Oncogene. 2013 Feb 28;32(9):1173-82. doi: 10.1038/onc.2012.128. Epub 2012 Apr 16.
Ref 4 FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity. Cells. 2023 Dec 6;12(24):2777.
Ref 5 Nuclear TIGAR mediates an epigenetic and metabolic autoregulatory loop via NRF2 in cancer therapeutic resistance. Acta Pharm Sin B. 2022 Apr;12(4):1871-1884.
Ref 6 Role of monocarboxylate transporter I/lactate dehydrogenase B-mediated lactate recycling in tamoxifen-resistant breast cancer cells. Arch Pharm Res. 2023 Dec;46(11-12):907-923.
Ref 7 Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3. Cancer Gene Ther. 2014 Jul;21(7):290-6. doi: 10.1038/cgt.2014.29. Epub 2014 Jun 13.
Ref 8 miR-449a Suppresses Tamoxifen Resistance in Human Breast Cancer Cells by Targeting ADAM22. Cell Physiol Biochem. 2018;50(1):136-149. doi: 10.1159/000493964. Epub 2018 Oct 2.
Ref 9 Long noncoding RNA H19 mediated the chemosensitivity of breast cancer cells via Wnt pathway and EMT process. Onco Targets Ther. 2018 Nov 9;11:8001-8012. doi: 10.2147/OTT.S172379. eCollection 2018.
Ref 10 MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem. 2008 Nov 7;283(45):31079-86. doi: 10.1074/jbc.M806041200. Epub 2008 Sep 12.
Ref 11 Metabolic reprograming confers tamoxifen resistance in breast cancer. Chem Biol Interact. 2021 Sep 25;347:109602. doi: 10.1016/j.cbi.2021.109602. Epub 2021 Jul 28.
Ref 12 Long non-coding RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR-18a-HIF1Alpha feedback regulatory loop. Tumour Biol. 2016 Nov;37(11):14733-14743. doi: 10.1007/s13277-016-5348-8. Epub 2016 Sep 15.
Ref 13 MiR-27b is epigenetically downregulated in tamoxifen resistant breast cancer cells due to promoter methylation and regulates tamoxifen sensitivity by targeting HMGB3. Biochem Biophys Res Commun. 2016 Sep 2;477(4):768-773. doi: 10.1016/j.bbrc.2016.06.133. Epub 2016 Jun 27.
Ref 14 A miR-26a/E2F7 feedback loop contributes to tamoxifen resistance in ER-positive breast cancer. Int J Oncol. 2018 Oct;53(4):1601-1612. doi: 10.3892/ijo.2018.4492. Epub 2018 Jul 19.
Ref 15 Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression. Cell Death Dis. 2016 Nov 3;7(11):e2454. doi: 10.1038/cddis.2016.361.
Ref 16 Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes. Cancer Lett. 2016 Aug 10;378(2):69-79. doi: 10.1016/j.canlet.2016.05.004. Epub 2016 May 6.
Ref 17 MicroRNA-519a is a novel oncomir conferring tamoxifen resistance by targeting a network of tumour-suppressor genes in ER+ breast cancer. J Pathol. 2014 Aug;233(4):368-79. doi: 10.1002/path.4363. Epub 2014 Jun 2.
Ref 18 MicroRNA 663b mediates TAM resistance in breast cancer by modulating TP73 expression. Mol Med Rep. 2018 Jul;18(1):1120-1126. doi: 10.3892/mmr.2018.9064. Epub 2018 May 23.
Ref 19 miR-375 inhibits cancer stem cell phenotype and tamoxifen resistance by degrading HOXB3 in human ER-positive breast cancer. Oncol Rep. 2017 Feb;37(2):1093-1099. doi: 10.3892/or.2017.5360. Epub 2017 Jan 9.
Ref 20 Shikonin reduces tamoxifen resistance through long non-coding RNA uc.57. Oncotarget. 2017 Sep 11;8(51):88658-88669. doi: 10.18632/oncotarget.20809. eCollection 2017 Oct 24.
Ref 21 Functional role of miR-10b in tamoxifen resistance of ER-positive breast cancer cells through down-regulation of HDAC4. BMC Cancer. 2015 Jul 24;15:540. doi: 10.1186/s12885-015-1561-x.
Ref 22 Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathwayMol Cancer Ther. 2014 May;13(5):1078-91. doi: 10.1158/1535-7163.MCT-13-0709. Epub 2014 Mar 14.
Ref 23 Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013 Dec;45(12):1446-51. doi: 10.1038/ng.2823. Epub 2013 Nov 3.
Ref 24 ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013 Dec;45(12):1439-45. doi: 10.1038/ng.2822. Epub 2013 Nov 3.
Ref 25 Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in estrogen receptor-positive metastatic breast cancer. Clin Chem. 2015 Jul;61(7):974-82. doi: 10.1373/clinchem.2015.238717. Epub 2015 May 15.
Ref 26 D538G mutation in estrogen receptor-Alpha: A novel mechanism for acquired endocrine resistance in breast cancer. Cancer Res. 2013 Dec 1;73(23):6856-64. doi: 10.1158/0008-5472.CAN-13-1197. Epub 2013 Nov 11.
Ref 27 Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients. Onco Targets Ther. 2015 Nov 11;8:3323-8. doi: 10.2147/OTT.S92443. eCollection 2015.
Ref 28 Emergence of constitutively active estrogen receptor-Alpha mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014 Apr 1;20(7):1757-1767. doi: 10.1158/1078-0432.CCR-13-2332. Epub 2014 Jan 7.
Ref 29 Droplet digital polymerase chain reaction assay for screening of ESR1 mutations in 325 breast cancer specimens. Transl Res. 2015 Dec;166(6):540-553.e2. doi: 10.1016/j.trsl.2015.09.003. Epub 2015 Sep 14.
Ref 30 The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis. Nat Genet. 2016 Aug;48(8):848-55. doi: 10.1038/ng.3602. Epub 2016 Jun 27.
Ref 31 Downregulated lncRNA ADAMTS9-AS2 in breast cancer enhances tamoxifen resistance by activating microRNA-130a-5p. Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1563-1573. doi: 10.26355/eurrev_201902_17115.
Ref 32 Long Non-Coding RNA (lncRNA) Urothelial Carcinoma-Associated 1 (UCA1) Enhances Tamoxifen Resistance in Breast Cancer Cells via Inhibiting mTOR Signaling Pathway. Med Sci Monit. 2016 Oct 21;22:3860-3867. doi: 10.12659/msm.900689.
Ref 33 [Urothelial carcinoma-associated 1 enhances tamoxifen resistance in breast cancer cells through competitively inhibiting miR-18a]. Beijing Da Xue Xue Bao Yi Xue Ban. 2017 Apr 18;49(2):295-302.
Ref 34 Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer. Mol Cancer. 2017 Oct 17;16(1):161. doi: 10.1186/s12943-017-0727-3.
Ref 35 MicroRNA-335-5p and -3p synergize to inhibit estrogen receptor alpha expression and promote tamoxifen resistance. FEBS Lett. 2017 Jan;591(2):382-392. doi: 10.1002/1873-3468.12538. Epub 2017 Jan 12.
Ref 36 Long non coding RNA UCA1 confers tamoxifen resistance in breast cancer endocrinotherapy through regulation of the EZH2/p21 axis and the PI3K/AKT signaling pathway. Int J Oncol. 2019 Mar;54(3):1033-1042. doi: 10.3892/ijo.2019.4679. Epub 2019 Jan 8.
Ref 37 MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer. Am J Transl Res. 2015 Oct 15;7(10):2115-26. eCollection 2015.
Ref 38 LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene. 2016 May;35(21):2746-55. doi: 10.1038/onc.2015.340. Epub 2015 Sep 14.
Ref 39 let-7 microRNAs induce tamoxifen sensitivity by downregulation of estrogen receptor Alpha signaling in breast cancer. Mol Med. 2011;17(11-12):1233-41. doi: 10.2119/molmed.2010.00225. Epub 2011 Jul 27.
Ref 40 Downregulation of miR-342 is associated with tamoxifen resistant breast tumors. Mol Cancer. 2010 Dec 20;9:317. doi: 10.1186/1476-4598-9-317.
Ref 41 Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer. Br J Cancer. 2010 Oct 12;103(8):1284-91. doi: 10.1038/sj.bjc.6605884. Epub 2010 Sep 21.
Ref 42 Methylation patterns of genes coding for drug-metabolizing enzymes in tamoxifen-resistant breast cancer tissues. J Mol Med (Berl). 2010 Nov;88(11):1123-31. doi: 10.1007/s00109-010-0652-z. Epub 2010 Jul 14.
Ref 43 Breast cancer cell resistance to hormonal and targeted therapeutics is correlated with the inactivation of the NR6A1 axis. Cancer Drug Resist. 2024 Nov 23;7:48.
Ref 44 Molecular mechanisms of secondary imatinib resistance in patients with gastrointestinal stromal tumors. J Cancer Res Clin Oncol. 2010 Jul;136(7):1065-71. doi: 10.1007/s00432-009-0753-7. Epub 2009 Dec 31.
Ref 45 The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor ModelsMol Cancer Ther. 2015 Apr;14(4):931-40. doi: 10.1158/1535-7163.MCT-14-0833. Epub 2015 Jan 30.
Ref 46 Phase II trial of gefitinib and everolimus in advanced non-small cell lung cancer. J Thorac Oncol. 2010 Oct;5(10):1623-9. doi: 10.1097/JTO.0b013e3181ec1531.
Ref 47 PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activityMol Cancer Ther. 2011 Nov;10(11):2189-99. doi: 10.1158/1535-7163.MCT-11-0185. Epub 2011 Jul 12.
Ref 48 Molecular Basis for Necitumumab Inhibition of EGFR Variants Associated with Acquired Cetuximab ResistanceMol Cancer Ther. 2018 Feb;17(2):521-531. doi: 10.1158/1535-7163.MCT-17-0575. Epub 2017 Nov 20.
Ref 49 Sodium/glucose cotransporter 1-dependent metabolic alterations induce tamoxifen resistance in breast cancer by promoting macrophage M2 polarization. Cell Death Dis. 2021 May 18;12(6):509.
Ref 50 Inverse FASN and LDHA correlation drives metabolic resistance in breast cancer. J Transl Med. 2024 Jul 24;22(1):676.

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