Long Non-coding RNA UCA1 Regulated Cell Cycle Distribution Via CREB Through PI3-K Dependent Pathway in Bladder Carcinoma Cells

Long non-coding RNA urothelial carcinoma associated 1 (UCA1) promotes human bladder cancer cell proliferation, but the underlying mechanism remains unknown. After knocking down of UCA1 in BLZ-211 cells, several cell cycle-related genes (CDKN2B, EP300 and TGFβ-2) were screened by microarray assay and validated by real-time PCR. Interestingly, in western blot analysis, p300 (encoded by EP300) and its coactivator cAMP response element-binding protein (CREB) level were significantly down-regulated. Both suppression of UCA1 expression by shRNA in BLZ-211 cells and ectopic expression of UCA1 in UMUC-2 cells showed that UCA1 alteration paralleled to the expression and phosphorylation of CREB, and UCA1 obviously influenced AKT expression and activity. Furthermore, in BLZ-211 cells, cell cycle progression was greatly reduced after PI3-K pathway was blocked by LY294002, indicating that UCA1 affected cell cycle progression through CREB. Taken together, we concluded that UCA1 regulated cell cycle through CREB via PI3K-AKT dependent pathway in bladder cancer.