title: MiR-129 regulates cisplatin-resistance in human gastric cancer cells by targeting P-gp.
abstract: Development of multiple drug resistance (MDR) to chemotherapy is the major reason for the failure of gastric cancer (GC) treatment. P-glycoprotein (P-gp), which is encoded by MDR gene 1, as one of the mechanisms responsible for MDR. Mounting evidence has demonstrated that the drug-induced dysregulation of microRNAs (miRNAs) function may mediate MDR in cancer cells. However, the underling mechanisms of miRNA-mediated MDR in GC remain unclear. Here, we found that miR-129 was downregulated in cisplatin-resistant GC tissues/cells. Our results also showed that overexpression of miR-129 decreased cisplatin-resistance in cisplatin-resistant GC cells, and miR-129 knockdown reduced chemosensitivity to cisplatin in cisplatin-sensitive GC cells. Furthermore, miR-129 activated the intrinsic apoptotic pathway via upregulating caspase-9 and caspase-3. Most importantly, we further confirmed that P-gp is the functional target of miR-129 by regulating cisplatin-resistance in GC cells. These results suggested that miR-129 reversed cisplatin-resistance through inhibiting the P-gp expression in GC cells.
authors.affiliation: Department of Thoracic Surgery, Changhai Hospital, Shanghai 200433, China.
authors.forename: Chaojing
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Thoracic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Department of Thoracic Surgery, Changhai Hospital, Shanghai 200433, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Changhai Hospital, Shanghai 200433, China. Electronic address: yanglixin_76@126.com.
authors.forename: Lixin
authors.initials: L
authors.lastname: Yang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D053453:Caspase 9 / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D053148:Caspase 3; D053453:Caspase 9; D002945:Cisplatin
keywords: Gastric cancer; Multiple drug resistance; P-glycoprotein; miR-129