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 (dsE-cad). Furthermore, this inhibitory effect was associated with relocalization of beta-catenin from the nucleus to the plasma membrane and decreased beta-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. (C) 2008 Elsevier Inc. All rights reserved.