Molecule Information

General Information of the Molecule (ID: Mol00336)

• Name: Transcription factor E2F1 (E2F1) ,Homo sapiens
• Synonyms: E2F-1; PBR3; Retinoblastoma-associated protein 1; RBAP-1; Retinoblastoma-binding protein 3; RBBP-3; pRB-binding protein E2F-1; RBBP3
• Molecule Type: Protein
• Gene Name: E2F1
• Gene ID: 1869
• Location: chr20:33675477-33686385[-]
• Uniprot ID: E2F1_HUMAN
• Ensembl ID: ENSG00000101412
• HGNC ID: HGNC:3113

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 5 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: BT549 cells; Breast; Homo sapiens (Human); CVCL_1092
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Trypan blue stain assay
• Mechanism Description: miR-302b overexpression enhances sensitivity to cisplatin in breast cancer cell lines, reducing cell viability and proliferation in response to the treatment. We also identified E2F1, a master regulator of the G1/S transition, as a direct target gene of miR-302b. E2F1 transcriptionally activates ATM, the main cellular sensor of DNA damage. Through the negative regulation of E2F1, miR-302b indirectly affects ATM expression, abrogating cell-cycle progression upon cisplatin treatment. Moreover miR-302b, impairs the ability of breast cancer cells to repair damaged DNA, enhancing apoptosis activation following cisplatin treatment.

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Leukemia [2]

• Sensitive Disease: Leukemia [ICD-11: 2B33.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: K562/A02 cells; Blood; Homo sapiens (Human); CVCL_0368
• Experiment for Molecule Alteration: RT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: The targeted upregulated expression of miR98 could decrease the proliferation of leukemia cells and improve the sensitivity to chemotherapeutics by inhibiting E2F1 expression.

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [3]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: QGY-7703 cells; Liver; Homo sapiens (Human); CVCL_6715
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: PLC cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vitro Model: FOCUS cells; Liver; Homo sapiens (Human); CVCL_7955
• In Vitro Model: YY-8103 cells; Liver; Homo sapiens (Human); CVCL_WY40
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: SRSF2 preferentially up-regulates the proapoptotic splicing form of caspase 2 (CASP2L) and sensitizes HCC cells to 5-FU. miR-193a-3p Dictates Resistance of Hepatocellular Carcinoma to 5-Fluorouracil via Repression of SRSF2 Expression.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [4]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Sp1/DAPK2 signaling signaling pathway; Inhibition; hsa05231
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MGC-803/OXA cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901/OXA cells; Gastric; Homo sapiens (Human); CVCL_B0A1
• In Vitro Model: SNU-5 cells; Gastric; Homo sapiens (Human); CVCL_0078
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR135a promotes gastric cancer progression and resistance to oxaliplatin. The mechanism whereby miR135a promotes GC pathogenesis appears to be the suppression of E2F1 expression and Sp1/DAPk2 pathway signaling.

Temozolomide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Glioma [5]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Down-regulation of miR-196b increased glioma cell sensitivity to TMZ and E2F1 decreased following transfection with miR-196b inhibitors.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.94E-01; Fold-change: -1.14E-01; Z-score: -5.05E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.40E-01; Fold-change: -1.95E-01; Z-score: -4.45E-01
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.35E-03; Fold-change: -1.02E+00; Z-score: -1.63E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.75E-01; Fold-change: -1.40E-02; Z-score: -6.69E-02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.70E-02; Fold-change: 1.16E-01; Z-score: 9.73E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.04E-05; Fold-change: 2.41E-01; Z-score: 1.39E+00

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.24E-06; Fold-change: 1.23E-01; Z-score: 5.52E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.21E-25; Fold-change: 2.79E-01; Z-score: 1.02E+00
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 8.77E-02; Fold-change: 4.13E-01; Z-score: 1.28E+00

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.31E-167; Fold-change: 5.27E-01; Z-score: 2.81E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.30E-11; Fold-change: 3.94E-01; Z-score: 1.15E+00

References

• Ref 1: miR-302b enhances breast cancer cell sensitivity to cisplatin by regulating E2F1 and the cellular DNA damage response. Oncotarget. 2016 Jan 5;7(1):786-97. doi: 10.18632/oncotarget.6381.
• Ref 2: Targeted regulation of MiR-98 on E2F1 increases chemosensitivity of leukemia cells K562/A02. Onco Targets Ther. 2017 Jun 29;10:3233-3239. doi: 10.2147/OTT.S126819. eCollection 2017.
• Ref 3: DNA methylation-regulated miR-193a-3p dictates resistance of hepatocellular carcinoma to 5-fluorouracil via repression of SRSF2 expression. J Biol Chem. 2012 Feb 17;287(8):5639-49. doi: 10.1074/jbc.M111.291229. Epub 2011 Nov 23.
• Ref 4: miR-135a promotes gastric cancer progression and resistance to oxaliplatin. Oncotarget. 2016 Oct 25;7(43):70699-70714. doi: 10.18632/oncotarget.12208.
• Ref 5: Downregulation of miR-196b Promotes Glioma Cell Sensitivity to Temozolomide Chemotherapy and Radiotherapy. Ann Clin Lab Sci. 2018 Nov;48(6):719-725.