MiR-425 involves in the development and progression of renal cell carcinoma by inhibiting E2F6

Q. Cai, A. Zhao, L.-G. Ren, J. Chen, K.-S. Liao, Z.-S. Wang, W. Zhang

Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, China. tcchr740@163.com

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• Oncology

OBJECTIVE: To investigate the effect of miR-425 on the proliferation and apoptosis of clear cell renal carcinoma (ccRCA) cells, and to explore the underlying mechanism.

PATIENTS AND METHODS: A total of 80 pairs of human clear cell renal carcinoma (ccRCA) and cancer-adjacent normal tissue samples were collected in this study. Human ccRCA cell line (786-O) and normal human kidney cell line (HK-2) were used in cellular research. The expression level of miR-425 was detected in ccRCA tissues and cells, respectively. Target genes of miR-425 were predicted by bioinformatics and verified by luciferase reporter gene assay. Moreover, the role of miR-425 in regulating E2F6 as well as its effect on the proliferation and apoptosis of ccRCA cells were detected.

RESULTS: Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) results showed that the expression of miR-425 was significantly decreased in ccRCA tissues and cells. The proliferation ability and cell cycle of 786-O cells were significantly inhibited after miR-425 overexpression. The percentage of cells in G0/G1 phase was remarkably increased, while the percentage of cells in S and G2/M phases was significantly decreased. Besides, the number of apoptotic cells was significantly increased in the miR-425 intervention group. On-line target gene prediction software indicated that E2F6 was the potential downstream target gene of miR-425. RT-PCR, Western blotting and luciferase reporter gene assay demonstrated that the expression of E2F6 was negatively regulated by miR-425. In addition, subsequent experiments showed that the up-regulation of E2F6 could suppress the inhibitory effect of miR-425 on the proliferation and apoptosis of ccRCA cells.

CONCLUSIONS: Our research demonstrated the inhibitory function of miR-425 in ccRCA. Therefore, the miR-425/E2F6 axis was expected to be one of the targets of ccRCA targeted therapy.

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