lncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21 expression in stomach cancer.

Abstract	Long non-coding RNAs (lncRNAs), which have evolved as important gene expression modulators, are involved in human malignancies. The down-regulation of lncRNA growth arrest specific transcript 5 (GAS5) has been reported in several cancers, however, the underlying mechanism of lncRNA GAS5 in stomach cancer is poorly understood. In this study, we found that lncRNA GAS5 had lower expression in stomach cancer tissues than the normal counterparts. lncRNA GAS5 was shown to interact with Y-box binding protein 1 (YBX1), and lncRNA GAS5 knockdown was shown to accelerate YBX1 protein turnover without affecting YBX1 transcription. lncRNA GAS5 down-regulation reduced the YBX1 protein level, which decreased YBX1-transactivated p21 expression and abolished G1 phase cell cycle arrest in stomach cancer. These results delineate a novel mechanism of lncRNA GAS5 in suppressing stomach carcinogenesis, and the lncRNA GAS5/YBX1/p21 pathway we discovered may provide useful targets for developing lncRNA-based therapies for stomach cancer.
Authors	Yongchao Liu, Jing Zhao, Wenhong Zhang, Jun Gan, Chengen Hu, Guangjian Huang, Ying Zhang
Journal	Scientific reports (Sci Rep) Vol. 5 Pg. 10159 (May 11 2015) ISSN: 2045-2322 [Electronic] England
PMID	25959498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cyclin-Dependent Kinase Inhibitor p21 GAS5 long non-coding RNA, human Mutant Proteins RNA, Long Noncoding Trans-Activators Y-Box-Binding Protein 1 YBX1 protein, human Sirolimus
Topics	Adult Aged Aged, 80 and over Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism) Down-Regulation (drug effects) Female G1 Phase Cell Cycle Checkpoints (genetics) Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Male Middle Aged Mutant Proteins (metabolism) Protein Binding (genetics) RNA, Long Noncoding (genetics, metabolism) Sirolimus (pharmacology) Stomach Neoplasms (genetics) Trans-Activators (metabolism) Y-Box-Binding Protein 1 (metabolism)

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