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.