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

Long non-coding RNAs (IncRNAs), which have evolved as important gene expression modulators, are involved in human malignancies. The down-regulation of IncRNA growth arrest specific transcript 5 (GAS5) has been reported in several cancers, however, the underlying mechanism of IncRNA GAS5 in stomach cancer is poorly understood. In this study, we found that IncRNA GAS5 had lower expression in stomach cancer tissues than the normal counterparts. IncRNA GAS5 was shown to interact with Y-box binding protein 1 (YBX1), and IncRNA GAS5 knockdown was shown to accelerate YBX1 protein turnover without affecting YBX1 transcription. IncRNA 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 IncRNA GAS5 in suppressing stomach carcinogenesis, and the IncRNA GAS5/YBX1/p21 pathway we discovered may provide useful targets for developing IncRNA-based therapies for stomach cancer.