title: Down-regulated expression of miR-134 contributes to paclitaxel resistance in human ovarian cancer cells.
abstract: MiR-134 has been reported to have a role in the development and progression of various cancers. In this study, we found that miR-134 expression was significantly decreased in chemo-resistant serous epithelial ovarian cancer (EOC) patients. Over-expression of miR-134 enhanced the sensitivity of SKOV3-TR30 cells to paclitaxel, and increased paclitaxel-induced apoptosis. Further, Pak2 was identified as a direct target of miR-134, and Pak2-specific siRNA increased cell inhibition rate and promoted paclitaxal-induced apoptosis. By regulating Pak2 expression, miR-134 could mediate Bad phosphorylation at Ser112 and Ser136, which affected cell survival and apoptosis. In conclusion, our findings indicate that repression of miR-134 and consequent up-regulation of Pak2 might contribute to paclitaxel resistance.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Shuang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: wm21st@hotmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; C515907:PAK2 protein, human; D054462:p21-Activated Kinases; D017239:Paclitaxel
keywords: Drug resistance; Ovarian cancer; Paclitaxel resistance; Pak2 gene; miR-134 expression