title: Reciprocal negative feedback loop between EZH2 and miR-101-1 contributes to miR-101 deregulation in hepatocellular carcinoma.
abstract: Although the tumor suppressive role of miR-101 is well documented in hepatocellular carcinoma (HCC), how the expression of miR-101 itself is regulated remains elusive. In the present study, we demonstrated that the miR-101 precursor pre-miR-101-1 could be regulated by an important epigenetic regulator, the enhancer of zeste homolog 2 (EZH2). Reporter gene assays revealed that ectopic expression of EZH2 inhibited the transcriptional activities of miR-101-1 promoter. Subsequent analyses revealed that miR-101-1 directly represses the expression of EZH2, and miR-101-1 and EZH2 form a reciprocal negative feedback loop as indicated by the fact that ectopic mature miR-101 could induce endogenous pre-miR-101-1 expression. This mature miR-101-induced pre-miR-101 expression was specific to pre-miR-101-1 and depended on EZH2 activities. Moreover, our results also demonstrated that similar antitumor effects can be achieved either by ectopic miR-101 or EZH2 silencing in HCC cells. These findings show that elevated EZH2 contributes to miR-101 deregulation in HCC and highlight the coordinated role of miR-101 and EZH2 in hepatocarcinogenesis.
authors.affiliation: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Zhuang
authors.affiliation: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Wuhe
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Mu
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Tu
authors.affiliation: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Detai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Hu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D000071221:Enhancer of Zeste Homolog 2 Protein; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D017930:Genes, Reporter; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014410:Tumor Stem Cell Assay
chemical_list: D020413:3' Untranslated Regions; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2