title: The miR-92b functions as a potential oncogene by targeting on Smad3 in glioblastomas.
abstract: MicroRNAs(miR) play an important role in cell growth, differentiation, proliferation and apoptosis, which can function either as oncogenes or as tumor suppressors in their effect on tumor growth. Smad3 is often underexpressed in very diverse types of malignant tumors and has an important tumor suppressive function; however, the underlying mechanism in solid cancer including glioblastomas(GBM) is not fully explored. The aim of this study is to explore the role of miR-92b in regulation of smad3 in GBM. In our study, we found that miR-92b expression was significantly increased in GBM tissues compared with normal brain tissues by Q-RT-PCR and in situ hybridization (P<0.01). However, expression of smad3 in GBM samples was significantly reduced compared with normal brain tissues by western blot and immunohistochemistry (P<0.05). Using 3'UTR luciferase reporter gene assay, we found that miR-92b directly affected smad3 expression in GBM cells by targeting the 3'-untranslated region. Silencing of miR-92b was able to significantly inhibit the viability of GBM cells in three GBM cell lines through up-regulating the TGF-beta/smad3/p21 signaling pathway in vitro. Furthermore, the tumor growth and the weight of U87 cells in the miR-92b inhibitor group were significantly inhibited when compared with that of the control group in vivo. Our data demonstrated that miR-92b may be considered as a tumor oncogene to promote GBM cell proliferation, and thus may serve as a potentially useful target for development of miRNA-based therapies in the future.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, 12# Wulumuqi middle Road, Shanghai 200040, China.
authors.forename: Zhe Bao
authors.initials: ZB
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Shao Jian
authors.initials: SJ
authors.lastname: Lin
authors.forename: Jiang Long
authors.initials: JL
authors.lastname: Lu
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.forename: Liang Fu
authors.initials: LF
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012844:Sincalide / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D008156:Luciferases; D012844:Sincalide
keywords: Glioblastoma; MicroRNA-92b; Oncogene; P21; Smad3