title: MicroRNA-101 sensitizes hepatocellular carcinoma cells to doxorubicin-induced apoptosis via targeting Mcl-1.
abstract: MicroRNAs (miRNAs/miRs) are important regulators of multiple cellular processes, and their dysregulation is a common event in tumorigenesis, including the development of hepatocellular carcinoma (HCC). Studies have shown that certain miRNAs are associated with resistance to chemotherapy or drug sensitization; however, the underlying mechanisms have largely remained elusive. Multiple drug resistance is a major barrier for the treatment of advanced HCC. In the present study, miR-101 was observed to be downregulated in a panel of HCC cell lines, suggesting that it has a tumor suppressor role. Furthermore, transfection of miR-101 significantly enhanced the cytotoxicity of doxorubicin to HepG2 cells. While overexpression of miR-101 did not influence the accumulation of doxorubicin, it promoted the apoptosis-inducing effect of doxorubicin in HepG2 cells. A bioinformatics analysis predicted that miR-101 directly targeted the 3'-untranslated region of myeloid cell leukemia 1 (Mcl-1), which was verified by a luciferase reporter assay. Finally, transfection of HepG2 cells with Mcl-1 expression plasmid inhibited apoptosis caused by doxorubicin plus miR-101 expression. In conclusion, the present study showed that miR-101 is a negative regulator of Mcl-1 in HCC, and the combination of miR-101 expression with doxorubicin may represent a novel approach for the treatment of HCC.
authors.affiliation: Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Haifei
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Deng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D004317:Doxorubicin