Upregulation of E‑cadherin expression mediated by a novel dsRNA suppresses the growth and metastasis of bladder cancer cells by inhibiting β-catenin/TCF target genes.

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 β-catenin was redistributed from the nucleus to the cell membrane following transfection of dsEcad‑346 and miR‑373. Additionally, the expression of β-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 β-catenin from nucleus to cell membrane and inhibiting the β-catenin/TCF target genes.

International journal of oncology. 2018 Mar 29 [Epub ahead of print]

Chuanchang Li, Jiaxuan Liu, Qingsong Zhang, Kai Cui, Qiangqiang Ge, Chenghe Wang, Zhong Chen

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Department of Pathology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.