title: miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL.
abstract: Glioblastoma multiforme (GBM) is the most malignant and common brain tumor; it is aggressive growth pattern means that GBM patients face a poor prognosis even when receiving the best available treatment modalities. In recent years, an increasing number of reports suggest that the discovery of microRNAs (miRNAs) might provide a novel therapeutic target for human cancers, including GBM. One miRNA in particular, microRNA-25 (miR-25), is overexpressed in several cancers, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-25 in GBM has not been totally elucidated. In this study, we demonstrated that miR-25 was significantly up-regulated in astrocytoma tissues and glioblastoma cell lines. In vitro studies further demonstrated that overexpressed miR-25 was able to promote, while its antisense oligos inhibited cell proliferation and invasion in U251 cells. Moreover, we identified neurofilament light polypeptide (NEFL) as a novel target molecule of miR-25. Also of note was the fact that NEFL was down-regulated with increased levels of miR-25 expression in human astrocytoma clinical specimens. In addition, via the mTOR signaling pathway, NEFL-siRNA could significantly attenuate the inhibitory effects of knockdown miR-25 on the proliferation and invasion of U251 cells. Overall, our results showed an important role for miR-25 in regulating NEFL expression in GBM, and suggest that miR-25 could be a potential target for GBM treatment.
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
authors.forename: Xianrui
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
authors.forename: Minhui
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
authors.forename: Chenfu
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Neurosurgery, Xiangya Hospital of Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, China. jiangwxxyyy@gmail.com.
authors.forename: Weixi
authors.initials: W
authors.lastname: Jiang
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C543351:MIRN25 microRNA, human; D035683:MicroRNAs; D016900:Neurofilament Proteins; D034741:RNA, Small Interfering; C044882:neurofilament protein L; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Cell proliferation and invasion; Glioblastoma; NEFL; miR-25