title: 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.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gan
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Chengen
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Guangjian
authors.initials: G
authors.lastname: Huang
authors.affiliation: 1] Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China [2] Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C561567:GAS5 long non-coding RNA, human; D050505:Mutant Proteins; D062085:RNA, Long Noncoding; D015534:Trans-Activators; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D020123:Sirolimus