MiR-182 affects renal cancer cell proliferation, apoptosis, and invasion by regulating PI3K/AKT/mTOR signaling pathway

J.-H. Fu, S. Yang, C.-J. Nan, C.-C. Zhou, D.-Q. Lu, S. Li, H.-Q. Mu

Department of Urology, Dongyang People’s Hospital, Dongyang, Zhejiang, China. xiaoxinnant@126.com

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• Oncology

OBJECTIVE: PI3K/AKT/mTOR signaling pathway plays a crucial role in tumorigenesis and development. It was shown that mTOR overexpression was associated with the pathogenesis of renal cancer. Down-regulation of MiR-182 was found in renal carcinoma tissue. This study thus aims to investigate the influence of miR-182 in regulating mTOR expression and renal carcinoma cell proliferation, invasion, and apoptosis.

PATIENTS AND METHODS: The targeted regulatory relationship between miR-182 and mTOR was tested by dual luciferase assay. Renal carcinoma tissue and benign renal tissue were collected to detect miR-182 and mTOR expressions. MiR-182, mTOR, p-mTOR, and Survivin levels were compared between HK-2 and A498 cells. Renal carcinoma A498 cells were divided into four groups, including miR-NC, anti-miR-182 mimic, si-NC, and si-mTOR groups. Cell apoptosis and proliferation were evaluated by flow cytometry. Cell invasion was determined by transwell assay.

RESULTS: Bioinformatics analysis revealed the complementary relationship between miR-182 and the 3’-UTR of mTOR mRNA. The level of miR-182 was significantly reduced, while mTOR expression was upregulated in renal carcinoma tissue compared with that in benign lesion, which was associated with TNM stage. MiR-182 expression was markedly declined, whereas mTOR, p-mTOR, and Survivin levels were apparently upregulated in A498 cells compared with that in HK-2 cells. The treatment of miR-182 mimic or si-mTOR transfection significantly downregulated mTOR, p-mTOR, and Survivin expressions, restrained cell proliferation and invasion, and enhanced cell apoptosis.

CONCLUSIONS: The decreasing level of miR-182 plays a role in enhancing mTOR expression and promoting renal carcinoma pathogenesis. Overexpression of miR-182 inhibited mTOR expression and weakened cell proliferation and invasion, which provides leads to the future therapy of renal cancer.

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