Open AccessSirtuin 5 regulates the proliferation, invasion and migration of prostate cancer cells through acetyl‐CoA acetyltransferase 1
Author(s) -
Guan Jingqian,
Jiang Xizi,
Gai Junda,
Sun Xiaodan,
Zhao Jinming,
Li Ji,
Li Yizhuo,
Cheng Ming,
Du Tengjiao,
Fu Lin,
Li Qingchang
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16016
Subject(s) - sirtuin , prostate cancer , cancer research , prostate , mapk/erk pathway , sirtuin 1 , cancer , sirt2 , cyclin d1 , biology , medicine , kinase , microbiology and biotechnology , downregulation and upregulation , nad+ kinase , biochemistry , enzyme , cell cycle , gene
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.