Oncotarget

Research Papers:

miR155 regulates the proliferation and invasion of clear cell renal cell carcinoma cells by targeting E2F2

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Yu Gao1,2,*, Xin Ma1,2,*, Yuanxin Yao1,2,*, Hongzhao Li1,2, Yang Fan1,2, Yu Zhang1,2, Chaofei Zhao1,2, Lei Wang1,2, Minghui Ma1,2, Zhengwei Lei1,2, Xu Zhang1,2

1Department of Urology, Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, 100853, P. R. China

2State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, 100853, P. R. China

*These authors contributed equally to this work

Correspondence to:

Xu Zhang, e-mail: xzhang@tjh.tjmu.edu.cn

Keywords: miR-155, proliferation and invasion, E2F2, clear cell renal cell carcinoma

Received: September 30, 2015     Accepted: February 18, 2016     Published: March 07, 2016

ABSTRACT

MicroRNAs (miRNAs) have emerged as critical modulators of carcinogenesis and tumor progression. In the present work, we sought to identify the biological function of miR-155 as well as its underlying mechanism in clear cell renal cell carcinoma (ccRCC). We examined the expression of miR-155 in clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-155 both in vitro and in vivo. The results of this analysis indicated that miR-155 activity was significantly upregulated in ccRCC tissues compared with the corresponding normal tissues. miR-155 was associated with ccRCC aggressiveness in both cell lines and clinical specimens, and a specific and inverse correlation between miR-155 and E2F2 expression was found in human ccRCC samples. Overexpression of miR-155 in 786-O cells decreased E2F2 expression while reduction of miR-155 by anti-miR-155 in ACHN cells elevated E2F2 expression. Re-expression of E2F2 in 786-O cells repressed the cell migration/invasion abilities elevated by miR-155, whereas knockdown of E2F2 in ACHN cells restored these cellular functions hampered by the miR-155 inhibitor. Using Western blot and luciferase reporter assays, we determined that E2F2 was a direct target of miR-155. Taken together, the in vitro and in vivo results demonstrate that miR-155 functions as a tumor-promoting miRNA by targeting E2F2 in ccRCC.