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Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152.
- Source :
-
Cancer letters [Cancer Lett] 2015 Apr 01; Vol. 359 (1), pp. 75-86. Date of Electronic Publication: 2015 Jan 08. - Publication Year :
- 2015
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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.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Apoptosis
Brain Neoplasms genetics
Brain Neoplasms metabolism
Brain Neoplasms pathology
Cell Movement
Cell Proliferation
Gene Expression Regulation, Neoplastic
Glioblastoma genetics
Glioblastoma metabolism
Glioblastoma pathology
Humans
Mice, Inbred BALB C
Mice, Nude
MicroRNAs genetics
Neoplasm Invasiveness
Neoplastic Stem Cells pathology
RNA, Long Noncoding genetics
RNA-Induced Silencing Complex metabolism
Time Factors
Transfection
Tumor Burden
Tumor Cells, Cultured
Up-Regulation
Xenograft Model Antitumor Assays
Brain Neoplasms therapy
Gene Knockdown Techniques
Genetic Therapy methods
Glioblastoma therapy
MicroRNAs metabolism
Neoplastic Stem Cells metabolism
RNA, Long Noncoding metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 359
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 25578780
- Full Text :
- https://doi.org/10.1016/j.canlet.2014.12.051