Molecule Information

General Information of the Molecule (ID: Mol01252)

• Name: X inactive specific transcript (XIST) ,Homo sapiens
• Synonyms: XIST
• Molecule Type: LncRNA
• Gene Name: LOC401093
• Gene ID: 7503
• Location: chrX:73820649-73852723[-]
• Ensembl ID: ENSG00000229807
• HGNC ID: HGNC:12810

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

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Nasopharyngeal carcinoma [1]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: HNE1 cells; Nasopharynx; Homo sapiens (Human); CVCL_0308
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Long non-coding RNA XIST modulates cisplatin resistance by altering PDCD4 and Fas-Lexpressions in human nasopharyngeal carcinoma HNE1 cells in vitro. XIST is up-regulated in HNE1/DDP cells, and down-regulation and up-regulation of XIST expression reduce and increase DDP resistance of the cells, respectively, possibly as a result of changes in the expressions of PDCD4 and Fas-L.

Disease Class: Non-small cell lung cancer [2]

• Resistant Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Knockdown of LncRNA-XIST enhances the chemosensitivity of NSCLC cells via suppression of autophagy. LncRNA-XIST inhibits the expression of miR17 to modulate ATG7 and LncRNA-XIST regulates autophagy through ATG7.

Disease Class: Lung adenocarcinoma [3]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/DDP cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Flow cytometric analysis; TUNEL assay; MTT assay; Colony formation assay
• Mechanism Description: LncRNA XIST overexpression in A549 cells increased their chemosensitivity to cisplatin both in vitro and in vivo by protecting cells from apoptosis and promoting cell proliferation. XIST functioned as competing endogenous RNA to repress let-7i, which controlled its down-stream target BAG-1.

Disease Class: Ovarian cancer [4]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• In Vitro Model: OVCA433 cells; Ovary; Homo sapiens (Human); CVCL_0475
• In Vitro Model: ALST cells; Ovary; Homo sapiens (Human); CVCL_W778
• In Vitro Model: OVCA432 cells; Ovary; Homo sapiens (Human); CVCL_3769
• In Vitro Model: OVCA 420 cells; Breast; Homo sapiens (Human); CVCL_3935
• In Vitro Model: OVCA3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vitro Model: OVCA429 cells; Ovary; Homo sapiens (Human); CVCL_3936
• In Vitro Model: OVCA633 cells; Ovary; Homo sapiens (Human); CVCL_W776
• In Vitro Model: OVCA680 cells; Ovary; Homo sapiens (Human); CVCL_W781
• In Vitro Model: OVCA702 cells; Ovary; Homo sapiens (Human); CVCL_W782
• In Vitro Model: OVCA810 cells; Ovary; Homo sapiens (Human); CVCL_W783
• Experiment for Molecule Alteration: qPCR; Microarray assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: One possible down-stream candidate is XIAP, which is the most potent direct inhibitor of caspases and apoptosis among all human IAP family proteins. Down-regulated expression of XIAP has been shown to induce apoptosis in chemoresistant human ovarian cancer cells. Down-regulation of XIST might increase the expression level of XIAP and block drug-induced apoptosis to cause resistance phenotype.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Non-small cell lung cancer [2]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• Cell Pathway Regulation: lncRNA-XIST/miR17 axis; Regulation; hsa05206
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Knockdown of LncRNA-XIST enhances the chemosensitivity of NSCLC cells via suppression of autophagy. LncRNA-XIST inhibits the expression of miR17 to modulate ATG7 and LncRNA-XIST regulates autophagy through ATG7.

Disease Class: Epithelial ovarian cancer [5]

• Sensitive Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p.

Ethanol

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Liver fibrogenesis [6]

• Resistant Disease: Liver fibrogenesis [ICD-11: DB94.Y]
• Resistant Drug: Ethanol
• Molecule Alteration: Up-regulation; Interaction
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HSCs; N.A.; .; N.A.
• In Vivo Model: male C57BL/6 mice model; Mus musculus
• Experiment for Molecule Alteration: Mimic assay; Luciferase assay; qRT-PCR; Western bloting analysis
• Experiment for Drug Resistance: MTT assay; Dual luciferase reporter assay
• Mechanism Description: XIST enhances ethanol-induced HSCs autophagy and activation via miR-29b/HMGB1 axis.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Malignant glioma [7]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: DNA damage repair signaling pathway; Activation; hsa03410
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: LN229 cells; Brain; Homo sapiens (Human); CVCL_0393
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: U118 cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: NHA; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; BrdU incorporation assay
• Mechanism Description: XIST was inversely correlated with miR29c, positively correlated with PS1, positively related with MGMT. XIST can inhibit miR29c expression by directly binding to miR29c and subsequently up-regulate the expression of SP1 and MGMT to promote the chemoresistance of glioma cells to TMZ.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Glioma [7]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: DNA mismatch repair pathway; Regulation; hsa03430
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: LN229 cells; Brain; Homo sapiens (Human); CVCL_0393
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: U118 cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: NHA; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; BrdU incorporation assay
• Mechanism Description: XIST can amplify the chemoresistance of glioma cell lines to TMZ through directly targetting miR29c via SP1 and MGMT. XIST/miR29c axis regulated glioma cell chemoresistance to TMZ through RNA mismatch repair pathway. XIST expression was up-regulated by miR29c inhibition while down-regulated by ectopic miR29, and XIST directly binds to miR29c to inhibit its expression, XIST and miR29c neatively regulates each other.

Clinical Trial Drug(s) 1 drug(s) in total

Abexinostat

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Breast cancer [8]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Abexinostat
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: HCC1954 cells; Breast; Homo sapiens (Human); CVCL_1259
• In Vitro Model: BrCa-MZ-01 cells; Breast; Homo sapiens (Human); CVCL_5495
• In Vitro Model: CRCM226X cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: CRCM311X cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: CRCM389X cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: CRCM392X cells; Breast; Homo sapiens (Human); N.A.
• In Vitro Model: S68 cells; Breast; Homo sapiens (Human); CVCL_5585
• In Vitro Model: Sk-BR-7 cells; Breast; Homo sapiens (Human); CVCL_5218
• In Vitro Model: SUM149 cells; Breast; Homo sapiens (Human); CVCL_3422
• In Vitro Model: SUM159 cells; Breast; Homo sapiens (Human); CVCL_5423
• In Vitro Model: Xist med cells; Breast; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Abexinostat induced CSC differentiation in low-dose sensitive BCLs, whereas it did not have any effect on the CSC population from high-dose sensitive BCLs. Abexinostat effect is mediated at the cellular level through the modulation of the CSC pool. Only the PDX with low Xist expression displayed a significant decrease of its CSC population after abexinostat treatment, whereas HDACi treatment induced an increase of the CSC population in PDX with high Xist expression.

Investigative Drug(s) 1 drug(s) in total

D-Glucose

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Type 2 diabetes mellitus [6]

• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Resistant Drug: D-Glucose
• Molecule Alteration: Down-regulation; Interaction
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ARPE-19 cells; Eye; Homo sapiens (Human); CVCL_0145
• Experiment for Molecule Alteration: Luciferase assay; qRT-PCR
• Mechanism Description: XIST, likely through competitive binding of hsa-miR-21-5p, provides protection against hyperglycemia-associated injury in human retinal pigment epithelial cells.

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: Brain
• The Specified Disease: Brain lower grade glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.03E-03; Fold-change: -8.69E-02
• The Studied Tissue: Brain
• The Specified Disease: Glioblastoma multiforme
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.73E-02; Fold-change: 1.19E-01

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung adenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.62E-04; Fold-change: -9.99E-02
• The Studied Tissue: Lung
• The Specified Disease: Lung squamous cell carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.50E-03; Fold-change: 1.24E-01

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian serous cystadenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.14E-84; Fold-change: 3.41E-01

References

• Ref 1: [Long non-coding RNA XIST modulates cisplatin resistance by altering PDCD4 and Fas-Lexpressions in human nasopharyngeal carcinoma HNE1 cells in vitro]. Nan Fang Yi Ke Da Xue Xue Bao. 2019 Mar 30;39(3):357-363. doi: 10.12122/j.issn.1673-4254.2019.03.15.
• Ref 2: Knockdown of lncRNA-XIST enhances the chemosensitivity of NSCLC cells via suppression of autophagy. Oncol Rep. 2017 Dec;38(6):3347-3354. doi: 10.3892/or.2017.6056. Epub 2017 Oct 24.
• Ref 3: LncRNA XIST promotes human lung adenocarcinoma cells to cisplatin resistance via let-7i/BAG-1 axis. Cell Cycle. 2017;16(21):2100-2107. doi: 10.1080/15384101.2017.1361071. Epub 2017 Sep 29.
• Ref 4: Relationship of XIST expression and responses of ovarian cancer to chemotherapy. Mol Cancer Ther. 2002 Aug;1(10):769-76.
• Ref 5: Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p. J Gynecol Oncol. 2018 Nov;29(6):e99. doi: 10.3802/jgo.2018.29.e99.
• Ref 6: Long noncoding RNA XIST enhances ethanol-induced hepatic stellate cells autophagy and activation via miR-29b/HMGB1 axisIUBMB Life. 2019 Dec;71(12):1962-1972. doi: 10.1002/iub.2140. Epub 2019 Aug 16.
• Ref 7: LncRNA-XIST interacts with miR-29c to modulate the chemoresistance of glioma cell to TMZ through DNA mismatch repair pathway. Biosci Rep. 2017 Sep 7;37(5):BSR20170696. doi: 10.1042/BSR20170696. Print 2017 Oct 31.
• Ref 8: The histone deacetylase inhibitor abexinostat induces cancer stem cells differentiation in breast cancer with low Xist expression. Clin Cancer Res. 2013 Dec 1;19(23):6520-31. doi: 10.1158/1078-0432.CCR-13-0877. Epub 2013 Oct 18.