SIRT4 Works As A Tumor Suppressor By Impeding Cell Proliferation And Invasion In Prostate Cancer Cells

Background: Prostate cancer is one of the frequently diagnosed cancers globally and the second primary cause of cancer-related deaths among men in the United State.Compared to white men,African men are more prone and likely to be diagnosed at the late stage of prostate cancer and also have a higher mortality rate.The incidence of prostate cancer increases with age.In 2018,the newly registered prostate cancer cases in the world accounted for approximately 7.1% of all new cancer cases among men.Prostate cancer,therefore,remains a major global health problem exploring the molecular mechanism of prostate cancer pathogenesis is still very essential for the development of novel and effective treatment.Sirtuin family consists of SIRT1-SIRT7 and plays an important role in different cellular processes such as apoptosis,mitochondrial biosynthesis,lipid metabolism,fatty acid oxidation,cellular stress response,insulin secretion,and aging.Studies have shown that SIRT4 can suppress and inhibits the growth,proliferation,and transformation of tumor cells such as colorectal and gastric tumors by suppressing glutamine anaplerosis,but no research reveals the role and function SIRT4 plays in the development of prostate cancer.Objectives: To elucidate the expression of SIRT4 in prostate cancer and to study its role in impeding cell proliferation and invasion and its underlying mechanism.Methods: Real-time quantitative reverse transcription-polymerase chain reaction(RT-q PCR)technology was used to detect SIRT4 gene expression in normal cells and LNCa P cells.SIRT4 plasmid was inserted into LNCa P cells by cell transfection technology.The CCK-8 method was used to detect changes in the proliferation of LNCa P cells in different groups.Transwell technology was used to detect changes in cell invasion ability.The expression of KLK3,P53,GLUD-1,and m TOR was detected by Western blot experiments and RT-q PCR technology.Results: The result of RT-q PCR suggested that SIRT4 expression was down-regulated in prostate cancer cells compared to normal cells.CCK-8 experiment results suggest that overexpression of the SIRT4 gene inhibits the proliferation of LNCa P prostate cancer cells.Besides,the transwell experimental results reveal that overexpression of SIRT4 gene inhibits the invasion of LNCa P prostate cancer cells.WESTERN BLOT and RT-q PCR results obtained indicated that the expressions of SIRT4 related genes KLK3 and GLUD-1 were down-regulated in the overexpressed SIRT4 group,and the expressions of P53 and m TOR genes were up-regulated in the SIRT4 overexpression group.The difference was statistically significant(P <0.05).Conclusions: In this study,we found that SIRT4 expression was significantly decreased in prostate cancer cell lines LNCa P Also overexpression of SIRT4 inhibits the proliferation and invasion of prostate malignant cells and the impact on SIRT4-related genes KLK3,GLUD-1,m TOR,P53 may be its potential mechanism.