长链非编码 RNA UCA1 通过 CREB 调控膀胱癌细胞周期分布，该调控途径依赖于 PI3-K。
Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells.
机构信息
Center for Molecular Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, 76 West Yanta Road, 710061 Xi'an, China.
出版信息
Gene. 2012 Mar 15;496(1):8-16. doi: 10.1016/j.gene.2012.01.012. Epub 2012 Jan 20.
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.
长链非编码 RNA 膀胱癌相关 1 号（UCA1）可促进人膀胱癌细胞增殖，但具体机制尚不清楚。在 BLZ-211 细胞中敲低 UCA1 后，通过微阵列分析筛选出几个细胞周期相关基因（CDKN2B、EP300 和 TGFβ-2），并通过实时 PCR 进行验证。有趣的是，在 Western blot 分析中，p300（由 EP300 编码）及其共激活因子 cAMP 反应元件结合蛋白（CREB）水平显著下调。BLZ-211 细胞中 shRNA 对 UCA1 的抑制作用和 UMUC-2 细胞中 UCA1 的异位表达均表明，UCA1 的改变与 CREB 的表达和磷酸化平行，并且 UCA1 明显影响 AKT 的表达和活性。此外，在 BLZ-211 细胞中，PI3-K 通路被 LY294002 阻断后，细胞周期进程大大减少，表明 UCA1 通过 CREB 影响细胞周期进程。综上所述，我们得出结论，UCA1 通过 PI3K-AKT 依赖性途径通过 CREB 调节膀胱癌中的细胞周期。
Zotero 插件