title: Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell.
abstract: Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of patients with advanced liver cancer. However, acquisition of cisplatin resistance is common in patients with hepatocellular carcinoma (HCC), and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-130a levels were significantly increased in HCC patients treated with cisplatin-based chemotherapy. miR-130a levels were also higher in cisplatin-resistant Huh7 cells than in Huh7 cells. Overexpression of miR-130a contributed to cisplatin resistance in Huh7 cell, whereas knockdown of miR-130a overcame cisplatin resistance in cisplatin-resistant Huh7 cell. We further demonstrated that upregulated miR-130a directly inhibited expression of tumor suppressor gene RUNX3, which resulted in activation of Wnt/β-catenin signaling and increased drug resistance. These data suggest that miR-130a/RUNX3/Wnt signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.
authors: Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People's Republic of China.
authors: Ning
authors: N
authors: Xu
authors: Conghuan
authors: C
authors: Shen
authors: Yi
authors: Y
authors: Luo
authors: Lei
authors: L
authors: Xia
authors: Feng
authors: F
authors: Xue
authors: Qiang
authors: Q
authors: Xia
authors: Jianjun
authors: J
authors: Zhang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis*; D019008:Drug Resistance, Neoplasm; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D060449:Wnt Signaling Pathway
chemical_list: D000970:Antineoplastic Agents; D050677:Core Binding Factor Alpha 3 Subunit; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; C493729:Runx3 protein, human; D002945:Cisplatin