title: miR-25 promotes glioma cell proliferation by targeting CDKN1C.
abstract: MicroRNAs (miRNA) have oncogenic or tumor-suppressive roles in the development and growth of human glioma. Glioma development is also associated with alteration in the activities and expression of cell cycle regulators, and miRNAs are emerging as important regulators of cell cycle progression. Here, we show that miR-25 is overexpressed in 91% of examined human glioma tissues and 4 out of 6 human glioma cell lines. MiR-25 increases cell proliferation in two independent glioma cell lines. Ectopic expression of miR-25 was found to reduce CDKN1C protein levels by directly targeting its 3'-untranslated region (UTR). Notably, ablation of endogenous miR-25 rescued CDKN1C expression and significantly decreased glioma cell proliferation by facilitating normal cell cycle progression. Our clinical investigation found CDKN1C and miR-25 levels were inversely correlated. Lastly, downregulation of CDKN1 by siRNA blocked the activity of miR-25 on promoting glioma cell proliferation. Overall, our results for the first time show an oncogenic role of miR-25 in human glioma by targeting CDKN1C and that miR-25 could potentially be a therapeutic target for glioma intervention.
authors.affiliation: Department of Neurology, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China.
authors.forename: Xuhai
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Health Care, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Tian
authors.affiliation: Department of Heath Care, The Children Hospital of Harbin City, Harbin, Heilongjiang, China.
authors.forename: Dongkai
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jiahang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Department of Medical Service Management, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: wgz1188@163.com.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: guomian_hyd@163.com.
authors.forename: Mian
authors.initials: M
authors.lastname: Guo
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D015854:Up-Regulation / Q000235:genetics
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; C543351:MIRN25 microRNA, human; D035683:MicroRNAs
keywords: CDK; CDKN1C; Cell cycle; Cyclin; Glioma; miR-25