TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000371199
  • Gene Name:XIAP
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:ovarian cancer
  • Tissue:The HEK293T (293T) cell line

Other information

  • Title:microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of XIAP.
  • Journal:Br J Cancer
  • Published:2017
  • PubMed ID:27875524
  • Abstract:Background:microRNAs (miRNAs) have regulatory roles in various cellular processes, including apoptosis. Recently, X-linked inhibitor of apoptosis protein (XIAP) has been reported to be dysregulated in epithelial ovarian cancer (EOC). However, the mechanism underlying this dysregulation is largely unknown. Methods:Using bioinformatics and a literature analysis, a panel of miRNAs dysregulated in EOC was chosen for further experimental confirmation from hundreds of miRNAs that were predicted to interact with the XIAP 3＇UTR. A dual-luciferase reporter assay was employed to detect the interaction by cellular co-transfection of an miRNA expression vector and a reporter vector with the XIAP 3＇UTR fused to a Renilla luciferase reporter. DAPI and TUNEL approaches were used to further determine the effects of an miR-137 mimic and inhibitor on cisplatin-induced apoptosis in ovarian cancer cells. Results:We identified eight miRNAs by screening a panel of dysregulated miRNAs that may target the XIAP 3＇UTR. The strongest inhibitory miRNA, miR-137, suppressed the activity of a luciferase reporter gene fused with the XIAP 3＇UTR and decreased the levels of XIAP protein in SKOV3 ovarian cancer cells. Furthermore, forced expression of miR-137 increased cisplatin-induced apoptosis, and the depressed expression of miR-137 decreased cisplatin-induced apoptosis in SKOV3 and primary EOC cells. Consistently, the disruption of miR-137 via CRISPR/Cas9 inhibited apoptosis and upregulated XIAP in A2780 cells. Furthermore, the effect of miR-137 on apoptosis could be rescued by XIAP in SKOV3 cells. In addition, miR-137 expression is inversely correlated with the level of XIAP protein in both ovarian cancer tissues and cell lines. Conclusions:Our data suggest that multiple miRNAs can regulate XIAP via its 3＇UTR. miR-137 can sensitise ovarian cancer cells to cisplatin-induced apoptosis, providing new insight into overcoming drug resistance in ovarian cancer.
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