title: MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells.
abstract: Growing evidence has demonstrated that the aberrant expression of miRNA is a hallmark of malignancies, indicating the important roles of miRNA in the development and progression of cancer. MiR-7 is considered as a tumor suppressor miRNA in multiple types of cancer. However, the role of miR-7 in human hepatocellular carcinoma (HCC) and its underlying mechanism remain elusive. In this study, we found that overexpression of miR-7 arrested cell cycle at G1 to S transition in HCC. By combinational use of bioinformatic prediction, reporter assay, quantitative real-time PCR (qRT-PCR) and Western blot, we confirmed that CCNE1, an important mediator in G1/S transition is one of new direct target genes of miR-7. Further studies revealed that silencing of CCNE1 recapitulated the effects of miR-7 overexpression, whereas enforced expression of CCNE1 reversed the suppressive effects of miR-7 in cell cycle regulation. Finally, analysis of qRT-PCR showed a reciprocal relationship between miR-7 and CCNE1 in clinical cancer tissues and multiple types of tumor cell lines. These findings indicate that miR-7 exerts tumor-suppressive effects in hepatocarcinogenesis through the suppression of oncogene CCNE1 expression and suggest a therapeutic application of miR-7 in HCC.
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Hu
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, PR China; The State Key Laboratory of Cancer Biology, Department of Immunology, The Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: agyang@fmmu.edu.cn.
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: ruizhang@fmmu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype
chemical_list: D019927:Cyclin E; D035683:MicroRNAs; D015513:Oncogene Proteins; C475820:CCNE1 protein, human; C549242:MIRN7-1 microRNA, human
keywords: Cell cycle regulation; Hepatocellular carcinoma; MicroRNA