Sirtuin 5 regulates the proliferation, invasion and migration of prostate cancer cells through acetyl-CoA acetyltransferase 1.

Abstract

Sirtuin 5 (SIRT5) is a NAD+ -dependent class III protein deacetylase, and its role in prostate cancer has not yet been reported. Therefore, to explore the diagnosis and treatment of prostate cancer, we investigated the effect of SIRT5 on prostate cancer. Sirtuin 5 was assessed by immunohistochemistry in 57 normal and cancerous prostate tissues. We found that the tissue expression levels of SIRT5 in patients with Gleason scores ≥7 were significantly different from those in patients with Gleason scores <7 (P < .05, R > 0). Further, mass spectrometry and pathway screening experiments showed that SIRT5 regulated the activity of the mitogen-activated protein kinase (MAPK) pathway, which in turn modulated the expression of MMP9 and cyclin D1. Being a substrate of SIRT5, acetyl-CoA acetyltransferase 1 (ACAT1) was regulated by SIRT5. SIRT5 also regulated MAPK pathway activity through ACAT1. These results revealed that SIRT5 promoted the activity of the MAPK pathway through ACAT1, increasing the ability of prostate cancer cells to proliferate, migrate and invade. Overall, these results indicate that SIRT5 expression is closely associated with prostate cancer progression. Understanding the underlying mechanism may provide new targets and methods for the diagnosis and treatment of the disease.

• Authors: Jingqian Guan, Xizi Jiang, Junda Gai, Xiaodan Sun, Jinming Zhao, Ji Li, Yizhuo Li, Ming Cheng, Tengjiao Du, Lin Fu, Qingchang Li
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 23 Pg. 14039-14049 (12 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 33103371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• ACAT1 protein, human
• Acetyl-CoA C-Acetyltransferase
• SIRT5 protein, human
• Sirtuins

Topics

• Acetyl-CoA C-Acetyltransferase (metabolism)
• Adult
• Aged
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Gene Expression
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• MAP Kinase Signaling System
• Male
• Middle Aged
• Neoplasm Grading
• Prostatic Neoplasms (etiology, metabolism, pathology)
• Protein Binding
• Sirtuins (genetics, metabolism)