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Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Int+J+Oncol 2018 ; 52 (6): 1815-26 Nephropedia Template TP
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Upregulation of E-cadherin expression mediated by a novel dsRNA suppresses the growth and metastasis of bladder cancer cells by inhibiting ?-catenin/TCF target genes #MMPMID29620261
Li C; Liu J; Zhang Q; Cui K; Ge Q; Wang C; Chen Z
Int J Oncol 2018[Jun]; 52 (6): 1815-26 PMID29620261show ga
Low expression levels of E-cadherin are correlated with poor prognosis in patients with bladder cancer (BCa). A small activating RNA (saRNA) targeting a specific promoter region can activate gene expression. In the present study, two small double-stranded RNAs (dsRNAs) targeting the promoter region of human E-cadherin were designed and synthesized, and the regulatory role of saRNAs in E-cadherin expression was investigated. The results of reverse transcription-quantitative polymerase chain reaction and western blotting demonstrated that transfection of dsEcad-346 into the BCa cell lines T24 and 5637 significantly activated E-cadherin expression. Furthermore, transfection of dsEcad-346 and miR-373 induced cell cycle arrest in G0/G1 phase, promoted apoptosis and significantly inhibited migration and invasion of BCa cells. Results of immunofluorescence and western blotting indicated that ?-catenin was redistributed from the nucleus to the cell membrane following transfection of dsEcad-346 and miR-373. Additionally, the expression of ?-catenin/T-cell factor complex (TCF) target genes (c-MYC, matrix metallopeptidase 2, cyclin D1) was suppressed following transfection of BCa cells with saRNA. Silencing of E-cadherin expression blocked the inhibitory effect of dsEcad-346 and miR-373 on BCa cells. In conclusion, a novel designed dsEcad-346 can activate the expression of E-cadherin in BCa cells. saRNA-mediated activation of E-cadherin expression inhibited the growth and metastasis of BCa cells by promoting the redistribution of ?-catenin from nucleus to cell membrane and inhibiting the ?-catenin/TCF target genes.