| Objective: Sirtuins family are defined as class III histone deacetylases,Recently,mammalian Silent information regulator two-4(SIRT4)has been reported to be a tumor suppressor gene in multiple cancers.However,the function of SIRT4 in clear cell renal cell carcinoma has not been reported before.The objective of the present study was to explore the potential role of SIRT4 in clear cell renal cell carcinoma.Methods: We estimated SIRT4 expression levels in clear cell renal cell carcinoma and its adjacent non-neoplastic tissue by bioinformatics data,Western blot,and RT?q PCR(Reverse transcription?quantitative polymerase chain reaction),the clinical and survival data were also collected and analyzed.In vitro study,clear cell renal cell carcinoma cell lines were transfected with SIRT4 specific si RNA or lentivirus to downregulate or overexpress the expression level of SIRT4.Then,the tumor cell proliferation capacity was assessed by 5-Ethynyl-2 ′-deoxyuridine assays,cell migration and invasion capacity were assessed by Transwell assays.Results: Our results indicated that the expression level of SIRT4 in clear cell renal cell carcinoma tissues was significantly lower than the corresponding normal tissues(P<0.001).Meanwhile,bioinformatics data and the result of western blot showed that low SIRT4 expression level was obviously involved with poor overall survival and advanced tumor stage in clear cell renal cell carcinoma patients.Biological experiments demonstrated that overexpression of SIRT4 significantly reduced the proliferation,migration and invasion ability of clear cell renal cell carcinoma cells.Conversely,downregulation of SIRT4 enhanced the proliferation,migration and invasion ability of clear cell renal cell carcinoma cells.Conclusion: These findings support that SIRT4 acts as a tumor suppressor in clear cell renal cell carcinoma,it might be a novel biomarker and new therapeutic target for clear cell renal cell carcinoma... |
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