MicroRNA-720 regulates E-cadherin–αE-catenin complex and promotes renal cell carcinoma

Nadeem S. Bhat, Melissa Colden, Altaf A. Dar, Sharanjot Saini, Prerna Arora, Varahram Shahryari, Soichiro Yamamura, Yuichiro Tanaka, Taku Kato, Shahana Majid, Rajvir Dahiya

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

miRNAs are implicated in regulating cancer progression and metastasis. Here, we show that miR-720 is positively associated with renal cell carcinoma (RCC). Elevated levels of miR-720 were observed in a panel of RCC cell lines and clinical tissues compared with nonmalignant cell line and normal samples. Loss of miR-720 function inhibited proliferation, migration, and invasion and induced apoptosis in RCC cell lines in vitro and repressed tumor growth in xenograft mouse models. Conversely, gain of miR-720 function in nonmalignant HK-2 cells induced procancerous characteristics. Silencing of miR-720 caused a marked induction in the levels of endogenous αE-catenin and E-cadherin protein levels in anti720 transfected cells compared with control, whereas miR-720 overexpression in RCC cell lines reduced activity of a luciferase reporter gene fused to the wild-type aE-catenin or E-cadherin 3'UTR compared with nonspecific 3'UTR control, indicating that αE-catenin–E-cadherin complex is a direct and functional target of miR-720 in RCC. We also observed attenuation of β-catenin, CD44, and Akt expression in RCC cells transfected with miR-720 inhibitor compared with control. Furthermore, miR-720 exhibited clinical significance in RCC. Expression of miR-720 significantly distinguished malignant from normal samples. Elevated miR-720 levels positively correlated with higher Fuhrman grade, pathologic stage, and poor overall survival of RCC patients. These findings uncover a new regulatory network in RCC involving metastasis-promoting miR-720 that directly targets expression of key metastasis-suppressing proteins E-cadherin and αE-catenin complex. These results suggest that therapeutic regulation of miR-720 may provide an opportunity to regulate EMT and metastasis in RCC.

Original languageEnglish (US)
Pages (from-to)2840-2848
Number of pages9
JournalMolecular cancer therapeutics
Volume16
Issue number12
DOIs
StatePublished - Dec 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Bhat, N. S., Colden, M., Dar, A. A., Saini, S., Arora, P., Shahryari, V., Yamamura, S., Tanaka, Y., Kato, T., Majid, S., & Dahiya, R. (2017). MicroRNA-720 regulates E-cadherin–αE-catenin complex and promotes renal cell carcinoma. Molecular cancer therapeutics, 16(12), 2840-2848. https://doi.org/10.1158/1535-7163.MCT-17-0400