Primary Exploration Of The Function And Mechanisms Of SIRT3 In Endometrial Carcinoma

Background:Endometrial cancer(EC)is one of the most common neoplasm of the female genital tract in the countries,and its incidence is increasing.Most endometrial cancers are diagnosed at an early localized stage and,with surgery,are often curable;5-year survival is approximately 95%.A large number of late-stages are still diagnosed,5-year survival ranges from 16%to 45%.They have few treatment options and a poor prognosis.Estrogen is a steroid hormone that binds to specific nuclear receptor ERs and activates downstream cascades.In type I endometrial cancer,estrogen causes high frequency mutations in mtDNA and increased mitochondrial synthesis to counteract apoptosis,increasing the risk of endometrial cancer.Silencing regulator 2 is a nicotine adenine dinucleotide-dependent histone deacetylase series.SIRT3 is a deacetylase localized in mitochondria and widely expressed in some metabolically tissues active such as myocardium,kidney,liver,and brown adipose tissue.It modifies other enzymes by deacetylation and participates in biological processes such as energy metabolism and antioxidants.Studies have found that the transcription level of SIRT3 is significantly inhibited in endometrial cancer.However,little is known about the mechanism of SIRT3 and endometrial cancer.The occurrence of type I endometrial cancer is closely related to estrogen.Therefore,this study explored the effect of SIRT3 on the malignant proliferation of type I endometrial cancer cells under the action of estrogen and its mechanism.Result:1.Data showed the mRNA expression of SIRT3 in EC tissues was significantly down-regulated compared with the normal tissues.Western blot analysis indicated that the SIRT3 protein expression was reduced in EC tumor tissues2.The expression of SIRT3 was down-regulated when estrogen incubation of ishikawa cells;There was a significant difference when the concentration was 1×10-6M.The expression of mRNA was significantly different when estrogen incubated for 6h,and for 24h that of protein.3.The MTT assay and cell wound scratch assay showed that SIRT3 overexpression significantly inhibited the proliferation and migration ability of ishikawa cells.4.Overexpression of SIRT3 reduced the mRNA expression of PI3KCA in ishikawa cells.In addition,western blot analysis also showed that PI3KCA protein expression was significantly decreased in ishikawa cells overexpressing SIRT3.Conclusion:the results demonstrated that SIRT3 expression in endometrial cancer cells and tissues decreased.SIRT3 suppresses the proliferation of endometrial cancer cells may via inhibition of PI3KCA expression.