ncRNA basic information
ncRNA ID:
MIMAT0000433
ncRNA Database:
miRBase
ncRNA Name:
miR-142-5p
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
qRT-PCR
ncRNA Target Gene:
BIRC3, BCL2, BCL2L2, MCL1, and XIAP
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00515 (APRD00359)
Drug Name:
Cisplatin
Drug Method:
The purpose of this study was to identify microRNAs (miRNAs) that bind to the 3 untranslated region (3UTR) of XIAP and have a role in chemoresistance in ovarian cancer. Using in silico analysis and literature review, a panel of miRNAs dysregulated in chemoresistant ovarian cancer was generated from hundreds of miRNAs that were predicted to target the XIAP 3UTR. Using a dual luciferase reporter assay and cellular co-transfection of a miRNA expression vector and a luciferase reporter fused to the XIAP 3UTR cognate miRNA binding site, we identified three miRNAs of which miR-142-5p had the greatest inhibitory effect. We found that overexpression of miR-142-5p suppressed XIAP expression by binding to its 3UTR in OVCAR3 and SKOV3 cells. Using a chemosensitivity assay, we found that in OVCAR3, SKOV3, and primary epithelial ovarian cancer (EOC) cells, overexpression or inhibition of miR-142-5p increased or suppressed their sensitivities to cisplatin respectively. In contrast, introducing XIAP without a 3UTR counteracted the effect of overexpressed miR-142-5p on cisplatin-induced apoptosis in OVCAR3 ovarian cancer cells. Furthermore, we found a negative correlation between miR-142-5p expression and XIAP protein levels in clinical samples from patients with EOC. Using clinical and miRNA expression data of more than 200 ovarian cancer patients treated with platinum-based chemotherapy from The Cancer Genome Atlas (TCGA) database, we found ovarian cancer patients with higher expression levels of miR-142-5p had longer median progression-free survival as compared to patients with lower miR-142-5p levels. We demonstrated that miR-142-5p also targeted four other anti-apoptotic genes, baculoviral IAP repeat-containing 3 (BIRC3), B-cell lymphoma-2 (BCL2), BCL2 like 2 (BCL2L2), and myeloid cell leukemia sequence 1 (MCL1) specifically. Transcriptome sequencing shed light on the essential apoptosis-related pathway in which miR-142-5p may be involved.
Drug Response:
sensitive
Cancer basic information
Cancer:
ovarian cancer
Tissue/Cell:
cell line (HEK-293T,OVCAR3,SKOV3)
Other information
Title:
miR-142-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes.
Journal:
Biochem Pharmacol
Published:
2019
PubMed ID:
30639456