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1. Oncol Rep. 2012 May 18. doi: 10.3892/or.2012.1823. [Epub ahead of print]

Altered microRNA expression in cisplatin-resistant ovarian cancer cells and
upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug

Yang L, Li N, Wang H, Jia X, Wang X, Luo J.

Department of Gynecology and Obstetrics, West China Second University Hospital,
Sichuan University, Chengdu, Sichuan 610041, P.R. China.

microRNAs (miRNAs) are short non-coding RNA molecules which are involved in the
regulation of various biological processes. Drug resistance has become a major
obstacle to successful chemotherapy of ovarian cancer. The aim of this study was
to investigate microRNA expression profiles in cisplatin-resistant ovarian cancer
cells and the role of miR-130a in regulating drug resistance. Analysis of
differentially expressed miRNAs between SKOV3 and SKOV3/CIS cells was assessed by
miRNA microarrays. Target prediction of miRNAs was determined with the help of
PicTar or TargetScan. Among these miRNAs, the expression of miR‑130a was verified
using qRT-PCR. The expression of MDR1 mRNA and P-glycoprotein (P-gp) after
cellular transfection was examined using qRT-PCR and western blotting,
respectively. Cisplatin sensitivity was detected by the MTT assay. We indentified
35 downregulated and 54 upregulated miRNAs in SKOV3/CIS compared to those in
SKOV3. We found that miR-130a was upregulated in SKOV3/CIS compared to the
parental SKOV3 cells, and PTEN was predicted to be the potential target of
miR-130a. Moreover, downregulation of miR-130a could inhibit MDR1 mRNA and P-gp
expression and overcome the cisplatin resistance in SKOV3/CIS cells, which
indicated that miR-130a may be associated with MDR1/P-gp-mediated drug resistance
and plays the role of an intermediate in drug-resistance pathways of
PI3K/Akt/PTEN/mTOR and ABC superfamily drug transporters in SKOV3/CIS cells. This
study provides important information for the development of targeted gene therapy
for reversing cisplatin resistance in ovarian cancer.

PMID: 22614869 [PubMed - as supplied by publisher]