Oncotarget

Research Papers:

MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer

Yue Zhang _, Fu-Jun Zhao, Li-Lan Chen, Luo-Qiao Wang, Kenneth P. Nephew, Ying-Li Wu and Shu Zhang

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Oncotarget. 2014; 5:12291-12303. https://doi.org/10.18632/oncotarget.2577

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Abstract

Yue Zhang1,*, Fu-Jun Zhao2,*, Li-Lan Chen1, Luo-Qiao Wang1, Kenneth P. Nephew3, Ying-Li Wu4, Shu Zhang1

1Department of Obstetrics and Gynecology, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, China

2Department of Urology, Shanghai First People’s Hospital, Shanghai Jiao-Tong University, Shanghai, 200080, China

3Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA

4Department of Pathophysiology, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China

*These authors contributed eqully to this work

Correspondence to:

Shu Zhang, e-mail: [email protected]

Ying-Li Wu, e-mail: [email protected]

Keywords: ovarian cancer, miR-373, Rab22a, invasion, metastasis

Received: July 19, 2014     Accepted: October 06, 2014     Published: November 07, 2014

ABSTRACT

Metastasis is major cause of mortality in patients with ovarian cancer. MiR-373 has been shown to play pivotal roles in tumorigenesis and metastasis; however, a role for miR-373 in ovarian cancer has not been investigated. In this study, we show that the miR-373 expression is down-regulated in human epithelial ovarian cancer (EOC) and inversely correlated with clinical stage and histological grade. Ectopic overexpression of miR-373 in human EOC cells suppressed cell invasion in vitro and metastasis in vivo, and the epithelial–mesenchymal transition process. Silencing the expression of miR-373 resulted in an increased migration and invasion of EOC cells. Using integrated bioinformatics analysis, gene expression arrays, and luciferase assay, we identified Rab22a as a direct and functional target of miR-373 in EOC cells. Expression levels of miR-373 were inversely correlated with Rab22a protein levels in human EOC tissues. Rab22a knockdown inhibited invasion and migration of EOC cells, increased E-cadherin expression, and suppressed the expression of N-cadherin. Moreover, overexpression of Rab22a abrogated miR-373-induced invasion and migration of EOC cells. Taken together, these results demonstrate that miR-373 suppresses EOC invasion and metastasis by directly targeting Rab22a gene, a new potential therapeutic target in EOC.


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