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

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) (GAS(5)) has been reported in several cancers, however, the underlying mechanism of lncRNA GAS(5) in stomach cancer is poorly understood. In this study, we found that lncRNA GAS(5) had lower expression in stomach cancer tissues than the normal counterparts. lncRNA GAS(5) was shown to interact with Y-box binding protein 1 (YBX1), and lncRNA GAS(5) knockdown was shown to accelerate YBX1 protein turnover without affecting YBX1 transcription. lncRNA GAS(5) 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 GAS(5) in suppressing stomach carcinogenesis, and the lncRNA GAS(5)/YBX1/p21 pathway we discovered may provide useful targets for developing lncRNA-based therapies for stomach cancer.