miR-106b-5p targets tumor suppressor gene SETD2 to inactive its function in clear cell renal cell carcinoma
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Wei Xiang1,*, Jun He1,*, Chao Huang1, Lejun Chen1, Dan Tao2, Xinchao Wu1, Miao Wang1, Gang Luo1, Xingyuan Xiao1, Fuqing Zeng1, Guosong Jiang1
1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province, Wuhan 430022, China
2Department of Oncology, The Fifth Hospital of Wuhan, Hubei Province, Wuhan 430050, China
*These authors have contributed equally to this work
Guosong Jiang, e-mail: firstname.lastname@example.org
Fuqing Zeng, e-mail: email@example.com
Keywords: clear cell renal cell carcinoma, SETD2, miR-106b-5p, p53, proliferation
Received: August 18, 2014 Accepted: December 15, 2014 Published: February 24, 2015
Inactivation of human SET domain containing protein 2 (SETD2) is a common event in clear cell renal cell carcinoma (ccRCC). However, the mechanism underlying loss of SETD2 function, particularly the post-transcriptional regulatory mechanism, still remains unclear. In the present study, we found that SETD2 was downregulated and inversely correlated with high expression of miR-106b-5p in ccRCC tissues and cell lines. Over-expression of miR-106b-5p resulted in the decreased mRNA and protein levels of SETD2 in ccRCC cells. In an SETD2 3’-UTR luciferase reporter system, miR-106b-5p downregulated the luciferase activity, and the effects were abolished by mutating the predicted miR-106b-5p binding site. Moreover, attenuation of miR-106b-5p induced cell cycle arrest at G0/G1 phase, suppressed cell proliferation, enhanced processing of caspase-3, and promoted cell apoptosis in ccRCC cells, whereas these effects were reversed upon knockdown of SETD2. In addition, transfection of miR-106b-5p antagomir resulted in the increased binding of H3K36me3 to the promoter of p53 and enhanced its activity, as well as upregulated the mRNA and protein levels of p53, and the effects were also abolished by cotransfection with si-SETD2. Collectively, our findings extend the knowledge about the regulation of SETD2 at the posttranscriptional level by miRNA and regulatory mechanism downstream of SETD2 in ccRCC.
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