title: Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152.
abstract: Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Great interest persists in useful therapeutic targets in GBM. Aberrant expression of long non-coding RNAs (lncRNAs) has been functionally associated with many cancers. Here, we elucidated the function and the possible molecular mechanisms of lncRNA XIST in human glioblastoma stem cells (GSCs). Our results proved that XIST expression was up-regulated in glioma tissues and GSCs. Functionally, knockdown of XIST exerted tumor-suppressive functions by reducing cell proliferation, migration and invasion as well as inducing apoptosis. The in vivo studies also showed that knockdown of XIST suppressed tumor growth and produced high survival in nude mice. Further, there was reciprocal repression between XIST and miR-152. Mechanistic investigations defined the direct binding ability of the predicted miR-152 binding site on the XIST. In addition, XIST and miR-152 are probably in the same RNA induced silencing complex (RISC). Finally, miR-152 mediated the tumor-suppressive effects that knockdown of XIST exerted. Taken together, these results provided a comprehensive analysis of XIST in GSCs and important clues for understanding the key roles of lncRNA-miRNA functional network in human glioma.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Teng
authors.affiliation: Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110001, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: liuyh@sj-hospital.org.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: C550856:MIRN152 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D034743:RNA-Induced Silencing Complex; C077885:XIST non-coding RNA
keywords: Glioblastoma; Long non-coding RNAs; MiR-152; Stem cells; XIST