Knockout of SIRT4 decreases chemosensitivity to 5-FU in colorectal cancer cells

Oncol Lett. 2018 Aug;16(2):1675-1681. doi: 10.3892/ol.2018.8850. Epub 2018 May 31.

Abstract

Previous studies demonstrated that sirtuin (SIRT) 4 is aberrantly expressed in human malignant tumors and is associated with poor prognosis in patients with colorectal cancer. However, the role of SIRT4 in the progression of human colorectal cancer (CRC) and in chemotherapy remains unclear. In the present study, the expression of SIRT4 in CRC tissues and the effect of SIRT4 on colorectal cancer proliferation, migration and invasion was investigated. Additionally, the effects of SIRT4 on the chemosensitivity in colorectal cancer cells and the underlying molecular mechanisms were also explored. The results demonstrated that SIRT4 expression is significantly downregulated in CRC tissues and cell lines. Downregulation of SIRT4 significantly increased tumor proliferation, migration and invasion. Additionally, downregulation of SIRT4 decreased the chemosensitivity of CRC cells by inhibiting cell apoptosis. Thus, these results suggest that SIRT4 may be a promising therapeutic target in CRC.

Keywords: apoptosis; chemosensitivity; colorectal cancer; sirtuin 4.