Up-regulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells

• Published in: Biochemical and biophysical research communications Vol. 375; no. 4; pp. 566 - 570
• Main Authors: Mao, Qiqi, Li, Yubing, Zheng, Xiangyi, Yang, Kai, Shen, Huafeng, Qin, Jie, Bai, Yu, Kong, Debo, Jia, Xiaolong, Xie, Liping
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.10.2008
• Subjects: 60 APPLIED LIFE SCIENCES; beta Catenin - metabolism; BLADDER; Bladder cancer; Cadherins - agonists; Cadherins - genetics; Cell Line, Tumor; Cell Membrane - metabolism; Cell Movement - drug effects; Cell Nucleus - metabolism; CELL PROLIFERATION; E-cadherin; Gene Expression - drug effects; GENE REGULATION; Humans; IN VITRO; Invasion; MONOCLINIC LATTICES; Neoplasm Invasiveness; NEOPLASMS; NEUTRON ACTIVATION ANALYSIS; NUCLEOTIDES; PROMOTERS; Protein Transport; PROTEINS; RNA; RNA, Double-Stranded - genetics; RNA, Double-Stranded - pharmacology; RNA, Double-Stranded - therapeutic use; Small activating RNA; Transcriptional Activation; Transfection; Up-Regulation; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Small activating RNA; E-cadherin; Bladder cancer; Invasion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.08.059

Recent studies have reported that chemically synthesized small duplex RNAs complementary to promoters of target genes can specifically induce gene expression in several cancer cell lines. Such dsRNA, referred to as small activating RNA (saRNA), are involved in the recently described phenomenon called RNA activation (RNAa). Recent findings show that saRNA can inhibit cell proliferation and viability via up-regulation of p21 WAF1/CIP1 (p21) in human bladder cancer cells. In the present study, we demonstrate that induction of E-cadherin expression by saRNA leads to suppression of migration and invasion of 5637 human bladder cancer cells in vitro. The elevated E-cadherin expression was confirmed at transcriptional and protein levels after transfection of a 21-nucleotide dsRNA targeting the E-cadherin promoter (dsEcad). Furthermore, this inhibitory effect was associated with relocalization of β-catenin from the nucleus to the plasma membrane and decreased β-catenin-mediated transactivation. These data suggest that activation of E-cadherin by saRNA may have a therapeutic benefit for bladder and other types of cancer.