title: Downregulation of miR-95-3p inhibits proliferation, and invasion promoting apoptosis of glioma cells by targeting CELF2.
abstract: Gliomas are the most common and aggressive types of tumors in human brain, of which the prognosis remains dismal because of their biological behavior. The involvement of miRNAs in tumorigenesis of various kinds of cancers drives us to explore new miRNAs related to gliomas. We measured expression level of miR‑95‑3p by qRT-PCR in human glioma and non-neoplasm brain tissues and found that higher level of miR‑95‑3p in glioma tissues of higher grade. Biological functions of miR‑95‑3p on glioma cells were investigated by MTT assay, flow cytometry and transwell assay. We discovered the cell lines transfected with miR‑95‑3p ASO (antisense oligonucleotide) had retarded proliferation and invasion but enhanced apoptosis ability. We searched on-line tool Targetscan and selected CELF (CUGBP- and ETR-3-like family 2) as a putative target. Luciferase reporter was employed to confirm the binding sites in 3'UTR region of CELF2 for miR‑95‑3p. The correlation between expression of CELF2 and miR‑95‑3p was determined by western blotting and qRT-PCR both in cell lines and human samples. Results showed CELF2 was a direct target of miR‑95‑3p and expression levels of CELF2 and miR‑95‑3p were negatively correlated. Finally, CELF2 largely abrogated the effects of miR‑95‑3p on proliferation, invasion and apoptosis of glioma cells in rescue experiments, which verified the role of CELF2 in miR‑95‑3p regulating glioma biological behavior. In conclusion, our data suggest the expression level of miR‑95‑3p is positively related to glioma grade and downregulation of miR‑95‑3p affects proliferation, invasion and apoptosis of glioma cells by targeting CELF2. We identified miR‑95‑3p as a putative therapeutic target and CELF2 as a potential tumor suppressor.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Bao-Hua
authors.initials: BH
authors.lastname: Jiao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050030, P.R. China.
authors.forename: Feng-Shi
authors.initials: FS
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Sheng-Kui
authors.initials: SK
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Cheng-Yong
authors.initials: CY
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Jian-Kai
authors.initials: JK
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
mesh_terms: D000328:Adult; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000067878:CELF Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D000067878:CELF Proteins; C117363:CELF2 protein, human; C575854:MIRN95 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins