title: microRNA-149 targets caspase-2 in glioma progression.
abstract: Malignant gliomas are the most common form of intrinsic primary brain tumors worldwide. Alterations in microRNAs play a role in highly invasive malignant glioma, but detail mechanism still unknown. In this study, the role and mechanism of microRNA-149 (miR-149) in glioma are investigated. We show that miR-149 is expressed at substantially higher levels in glioma than in normal tissues. Stable overexpression of miR-149 augments potent prosurvival activity, as evidenced by promotion of cell viability, inhibition of apoptosis, and induced xenografted tumor growth in vivo. We further show that Caspase-2 is identified as a functional target of miR-149 and expression of caspase-2 is inversely associated with miR-149 in vitro. In addition, miR-149 promotes tumor survival in the U87-MG and A172 cell lines and it targets caspase-2 via inactivation of the p53 and p21 pathways. There results support a special role for miR-149 by targeting Caspase-2 to impact on p53 signaling pathway. We speculate that miR-149 has distinct biological functions in p53 wild type cells and p53 mutation cells, and the mechanisms involved remain to be explored in future. Our study suggests that targeting miR-149 may be a novel therapy strategy for treating p53 wild type glioma tumors in humans.
authors.affiliation: Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Shen
authors.affiliation: Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Liao
authors.affiliation: Department of General Surgery, Zhongshan Hospital, General Surgery Institute, Fudan University, Shanghai 200032, China.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Huanjun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Zhongshan Hospital, General Surgery Institute, Fudan University, Shanghai 200032, China.
authors.forename: Houbao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Glycobiology and Glycochemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Ding
mesh_terms: D000328:Adult; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053143:Caspase 2 / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged
chemical_list: C551557:MIRN149 microRNA, human; D035683:MicroRNAs; C490360:CASP2 protein, human; D053143:Caspase 2; D003546:Cysteine Endopeptidases
keywords: caspase-2; glioma; microRNA-149; p53