SIRT1 promotes endometrial tumor growth by targeting SREBP1 and lipogenesis

Silent information regulator 1 (SIRT1) is involved in a number of cellular regulatory mechanisms affecting cellular life span, stress resistance, apoptosis and cellular metabolism. Recent studies have revealed that SIRT1 plays a dual role as a tumor suppressor and a tumor promoter in multiple stages of carcinogenesis. Increased lipogenesis has been found in cancer cells, sterol regulatory element binding protein 1 (SREBP1) are nuclear lipogenic transcription factors, which mainly regulate lipogenic processes by activating genes involved in fatty acid and triglyceride biosynthesis. In the present study, we detected expression of SIRT1 in endometrial cancer (EC) and illustrated the relationship between SIRT1 and SREBP1, which indicated that SIRT1 could stimulate endometrial tumor growth through the lipogenic pathway. Gene expression levels of SIRT1 were assayed using quantitative real-time PCR and protein expression levels were detected by western blotting. RNA interference was conducted in order to explore the subsequent effect on tumor cells and on the expression of SREBP1. Expression levels of SIRT1 in EC were found to be significantly higher than in normal endometrium. Knockdown of SIRT1 could downregulate expression of SREBP1 and suppress cell proliferation. These results demonstrated that SIRT1 may play a role as a tumor promoter in EC and can promote endometrial tumor growth by promoting lipogenesis. Our findings suggest that targeting SIRT1 may provide a theoretical basis for the management of EC.