title: Altered microRNA expression in cisplatin-resistant ovarian cancer cells             and upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug             resistance.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Yang
authors.forename: Ningwei
authors.initials: N
authors.lastname: Li
authors.forename: Hongjing
authors.initials: H
authors.lastname: Wang
authors.forename: Xibiao
authors.initials: X
authors.lastname: Jia
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Luo
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D046228:Microarray Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D013053:Spectrophotometry; D014162:Transfection; D015854:Up-Regulation
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin