title: MicroRNA-122 sensitizes HCC cancer cells to adriamycin and vincristine through modulating expression of MDR and inducing cell cycle arrest.
abstract: Hepatocellular carcinoma (HCC) is a hypervascular cancer characterized by rapid progression as well as resistance to conventional chemotherapy. It has been shown that microRNAs play critical roles in pathogenesis of HCC. MicroRNA-122 (miR-122) is a liver-specific microRNA and is frequently downregulated in HCC. In the present study, we investigated whether restoration of miR-122 in HCC cells could render cells sensitive to chemotherapeutic agents adriamycin (ADM) or vincristine (VCR). Our data showed that overexpression of miR-122 in HCC cells induced by adenovirus expressing miR-122 could render cell sensitive to ADM or VCR. Analysis of cell cycle distribution showed that the anti-proliferative effect of miR-122 is associated with increase of cell number in the G2/M phase. Moreover, treatment with Ad-miR122 and ADM or VCR resulted in high accumulation of HCC cells in G2/M phase. We further demonstrated that overexpression of miR-122 could modulate the sensitivity of the HCC cells to chemotherapeutic drugs through downregulating MDR related genes MDR-1, GST-π, and MRP, antiapoptotic gene Bcl-w and cell cycle related gene cyclin B1. Taken together, our findings demonstrated that combination of Ad-miR122 with chemotherapeutic agents inhibited HCC cell growth by inducing G2/M arrest and that this arrest is associated, at least in part, with reduced expression of MDR related genes and Cyclin B1.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Xia
authors.forename: Leina
authors.initials: L
authors.lastname: Ma
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Shan
authors.forename: Junjie
authors.initials: J
authors.lastname: Shen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Youhong
authors.initials: Y
authors.lastname: Cui
authors.forename: Xiuwu
authors.initials: X
authors.lastname: Bian
authors.forename: Ping
authors.initials: P
authors.lastname: Bie
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000256:Adenoviridae / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D056766:Cyclin G1 / Q000096:biosynthesis / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D014750:Vincristine / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; C534702:CCNG1 protein, human; D056766:Cyclin G1; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D014750:Vincristine; D004317:Doxorubicin