Promoter-associated endogenous and exogenous small RNAs suppress human bladder cancer cell metastasis by activating p21 CIP1/WAF1 expression
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Accumulating data suggest that micro RNAs (miRNAs) or double-stranded RNAs (dsRNAs) can activate gene expression by targeting promoters. The cyclin-dependent kinase inhibitor p21 CIP1/WAF1 (p21) has also been shown to suppress epithelial-mesenchymal transition (EMT) which plays a crucial role in the early stage of tumor metastases and invasiveness. In a previous study, we have reported that miR-370-5p is low-expressed in bladder cancer (BCa) tissues and cell lines. Here, we identified that miR-370-5p and sequence homology dsRNA (dsP21-555) fully complementary to promoter hold the potent abilities to induce p21 expression. Moreover, transfection of miR-370-5p or dsP21-555 into BCa cells remarkably inverts EMT-associated genes (increases epithelial cell makers E-cadherin and β-catenin, and decreases mesenchymal cell markers ZEB1 and Vimentin) expression mainly via regulating p21 expression. Besides, through manipulating p21, both the candidates can retard BCa cell migration and invasion. In summary, our results provide evidence that both endogenous and exogenous small RNAs may function to induce p21 expression by interacting with the similar promoter region and impede BCa metastasis.
Keywordsp21 Bladder cancer RNA activation Epithelial-mesenchymal transition Micro RNA Double-stranded RNA
This work was supported by the National Natural Science Foundation of China [grant number 81372759, China]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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- 1.Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: Cancer J Clin. 2011;61:69–90.Google Scholar
- 5.Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA: Cancer J Clin. 2014;64:9–29.Google Scholar
- 18.Huang V, Qin Y, Wang J, Wang XL, Place RF, Lin GT, et al. RNAa is conserved in mammalian cells. PLoS One. 2010;5.Google Scholar
- 19.Li Q, Li J, Wen T, Zeng W, Peng C, Yan S, et al. Overexpression of HMGB1 in melanoma predicts patient survival and suppression of HMGB1 induces cell cycle arrest and senescence in association with p21 (WAF1/CIP1) up-regulation via a p53-independent, Sp1-dependent pathway. Oncotarget. 2014;5:6387–403.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Place RF, Wang J, Noonan EJ, Meyers R, Manoharan M, Charisse K, et al. Formulation of small activating RNA into lipidoid nanoparticles inhibits xenograft prostate tumor growth by inducing p21 expression. Mol Ther-Nucl Acids. 2012;1.Google Scholar