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PMID: 26370254 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Gas5 Exerts Tumor-suppressive Functions in Human Glioma Cells by Targeting miR-222.

Molecular therapy : the journal of the American Society of Gene Therapy ·Vol. 23 ·No. 12 ·2015-12-00 ·Pages 1899-911

Zhao X, Wang P, Liu J, Zheng J, Liu Y, Chen J, Xue Y

Abstract

Aberrant expression of noncoding RNAs in glioma cells, including long noncoding RNAs (lncRNAs) and microRNAs, may participate in the progression of glioma. Encoded by Growth Arrest-Specific 5 (GAS5) gene, lncRNA Gas5 was reported to be a negative regulator for survival and proliferation of several cancers. Here, Gas5 is found to be downregulated in glioma specimens and U87 and U251 glioma cell lines. We showed that the introduction of Gas5 by plasmid transfection increased the expression of tumor suppressor Bcl-2-modifying factor (bmf) and Plexin C1 via directly targeting and reducing the expression of miR-222. Downregulated expression of miR-222 inhibited U87 and U251 cell proliferation and promoted the apoptosis by upregulating bmf. As downstream signaling molecules of bmf, Bcl-2 and Bax were involved in the process. Meanwhile, knockdown of miR-222 attenuated U87 and U251 cell migration and invasion by upregulating Plexin C1, and cofilin was a crucial regulator targeted by Plexin C1. Gas5 combined with the knockdown of miR-222 resulted in the smallest tumor volumes and the longest survivals of nude mice in vivo. In summary, we show that Gas5 suppresses tumor malignancy by downregulating miR-222, which may serve as a promising therapy for glioma.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Animals Apoptosis/genetics Cell Line, Tumor Cell Movement Cell Proliferation Down-Regulation Gene Expression Regulation, Neoplastic Genetic Therapy Glioma/genetics,therapy Humans Mice Mice, Nude MicroRNAs/genetics,metabolism RNA, Long Noncoding/genetics,metabolism Receptors, Virus/genetics,metabolism Transfection Up-Regulation Xenograft Model Antitumor Assays bcl-2-Associated X Protein/genetics,metabolism
Chemicals
Adaptor Proteins, Signal Transducing BAX protein, human BMF protein, human GAS5 long non-coding RNA, human MIRN222 microRNA, human MicroRNAs RNA, Long Noncoding Receptors, Virus VESPR semaphorin receptor bcl-2-Associated X Protein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zhao Xihe
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China. | Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
Wang Ping
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China. | Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
Liu Jing
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Zheng Jian
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Liu Yunhui
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Chen Jiajia
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China. | Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
Xue Yixue
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, People's Republic of China. | Institute of Pathology and Pathophysiology, China Medical University, Shenyang, People's Republic of China.
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Article Info
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
Abbr.
Mol Ther
ISSN
1525-0024
DOI
10.1038/mt.2015.170
Published
2015-12-00
Epub
2015-00-15
Pages
1899-911
Language
English
Region
United States
NLM ID
100890581
PMCID
PMC4700110
Subset
IM
External Links
PubMed source DOI: 10.1038/mt.2015.170 PMC Full Text View journal details
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