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2018 ; 52
(6
): 1815-1826
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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
): 1815-1826
PMID29620261
show 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.