title: miR-193b acts as a cisplatin sensitizer via the caspase-3-dependent pathway in HCC chemotherapy.
abstract: Mounting evidence suggests that microRNAs (miRNAs) play important roles in the development of cancer by targeting expression of tumor-related genes. In the present study, downregulation of miR-193b was observed in hepatocellular carcinoma (HCC) tissues and HCC cell lines by quantitative RT-PCR analyses, suggesting that miR-193b is a tumor-suppressor in HCC. More importantly, miR-193b significantly enhanced the cytotoxicity of cisplatin in HepG2 cells by targeting Mcl-1. Knockdown of the Mcl-1 gene by specific siRNA exhibited a function similar to miR-193b on sensitizing HepG2 cells to cisplatin-inducing cytotoxicity. Furthermore, the miR-193b-induced sensitization of HepG2 cells to cisplatin cytotoxicity was abolished by the transfection of Mcl-1 expression plasmid that lacked the 3'-untranslated region (3'-UTR). In addition, activation of caspase-3 was needed for sensitization by miR-193b to cisplatin-mediated cell death. Thus, the present study revealed the downregulation of miR-193b in HCC cells and illustrated a synergistic effect on cisplatin-induced apoptosis by targeting Mcl-1.
authors.affiliation: Cancer Research Institute of Medical College, University of Southern China, University Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, P.R. China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Cancer Research Institute of Medical College, University of Southern China, University Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, P.R. China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Chemotherapy Oncology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Xie
authors.affiliation: Cancer Research Institute of Medical College, University of Southern China, University Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, P.R. China.
authors.forename: Xiusheng
authors.initials: X
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D053148:Caspase 3; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C579095:MCL1 protein, human; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D002945:Cisplatin