Sirtuin 6 regulates the proliferation and survival of clear cell renal cell carcinoma cells via B-cell lymphoma 2.

Abstract

Sirtuin 6 (SIRT6) is a member of the third family of longevity proteins (SIRTs) that is involved in the development of different types of cancer. However, the potential role of SIRT6 in clear cell renal cell carcinoma (ccRCC) and its molecular mechanism have not yet been fully elucidated. Therefore, the present study aimed to investigate the association between SIRT6 and ccRCC, and to further examine the underlying mechanism of its effect on ccRCC proliferation, using bioinformatics analysis, and in vitro and in vivo experiments. The results of the present study demonstrated that SIRT6 was upregulated in ccRCC tissues. In addition, bioinformatics analysis revealed that high SIRT6 expression was closely associated with poor prognosis of patients with ccRCC. In vitro experiments demonstrated that silencing SIRT6 expression in ccRCC-derived 769-P and 786-O cells significantly inhibited their proliferation, migration and invasion. Consistent with these results, in vivo assays demonstrated that SIRT6 knockdown markedly attenuated tumor growth arising from 769-P cells. Furthermore, depletion of SIRT6 enhanced the sensitivity of ccRCC cells to cisplatin. Notably, silencing SIRT6 expression decreased B-cell lymphoma 2 (Bcl-2) expression and increased Bax expression, respectively. Taken together, these results suggest that SIRT6 acts as a proto-oncogene in ccRCC through the augmentation of the Bcl-2-dependent pro-survival pathway, and may be used as a therapeutic target for patients with ccRCC.