title: Knockdown of NEAT1 restrained the malignant progression of glioma stem cells by activating microRNA let-7e.
abstract: Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA, promotes oncogenesis in various tumors, including human gliomas. Herein, we studied the expression and function of NEAT1 in glioma stem cells (GSCs). Quantitative real-time PCR demonstrated that NEAT1 was upregulated in GSCs. NEAT1 knockdown inhibited GSC cell proliferation, migration and invasion and promoted GSC apoptosis. A potential binding region between NEAT1 and microRNA let-7e was confirmed by dual-luciferase assays. Upregulation of NEAT1 reduced the expression of let-7e, and there was reciprocal repression between NEAT1 and let-7e in an Argonaute 2-dependent manner. Let-7e expression was lower expression in glioblastoma tissues and GSCs than in normal brain tissues and cells. Restoration of let-7e suppressed tumor function by inhibiting proliferation, migration and invasion while promoting apoptosis in GSCs. NEAT1 knockdown and let-7e overexpression both reduced NRAS protein expression. NRAS was identified as a direct target of let-7e and promoted oncogenesis in GSCs. As NEAT1 promoted oncogenesis by downregulating let-7e expression, both of these genes could be considered for application in glioma therapy.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang 110004, People's Republic of China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110122, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000818:Animals; D017209:Apoptosis; D060565:Argonaute Proteins / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; C577276:NEAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C487931:mirnlet7 microRNA, human; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: NEAT1; NRAS; glioma stem cells; let-7e; lncRNAs