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

Abstract

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.

Nuclear translocation of β-catenin induced by E-cadherin endocytosis causes recurrent erosion of diabetic cornea

“…37 Under conditions of strong adhesion, b-catenin is stable and protected within the cadherin complex, forming a strong coupling structure and maintaining tight cell junctions. 36,38,39 Our study found that E-cadherin was degraded under elevated glucose, but the b-catenin in the cytoplasm did not increase. According to previous studies, there are two metabolic pathways after b-catenin is isolated from b-catenin/E-cadherin complex: 40,41 and differentiation.…”

Modulating the expression of tumor suppressor genes using activating oligonucleotide technologies as a therapeutic approach in cancer

“…CDH1 is a TSG that has gained attention for its potential to be upregulated using saRNAs and has been investigated in this context across many cancer types. 2 , 23 , 24 , 25 , 26 , 27 CDH1 encodes the transmembrane glycoprotein E-cadherin, which is involved in maintaining epithelial cell morphology via adherens junction connections. 67 Furthermore, E-cadherin is anchored to the cell’s cytoskeleton via an interaction with β-catenin, a key protein involved in the pro-proliferative Wnt signaling pathway.…”

“…(Refs. 2 , 23 , 24 , 25 , 26 , 27 ) VEZT Vezatin, adherens junctions transmembrane protein Transmembrane protein involved in maintaining adherens’ junctions. Gastric cancer In vitro Xie et al.…”