SIRT5 Directly Inhibits the PI3K/AKT Pathway in Prostate Cancer Cell Lines

被引：18

作者：

Choi, So Young ^{[1
]}

Jeon, Ju Mi ^{[1
]}

Na, Ann Yae ^{[1
]}

Kwon, Oh Kwang ^{[1
]}

Bang, In Hyuk ^{[2
]}

Ha, Yun-Sok ^{[3
]}

Bae, Eun Ju ^{[4
]}

Park, Byung-Hyun ^{[2
]}

Lee, Eun Hye ^{[5
]}

Kwon, Tae Gyun ^{[3
]}

Lee, Jun Nyung ^{[3
]}

Lee, Sangkyu ^{[1
]}

机构：

[1] Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, BK21 Plus KNU Multi Based Creat Drug Res Team, Daegu, South Korea

[2] Chonbuk Natl Univ, Med Sch, Dept Biochem & Mol Biol, Jeonju, South Korea

[3] Kyungpook Natl Univ, Sch Med, Dept Urol, 807 Hoguk Ro, Daegu 41405, South Korea

[4] Chonbuk Natl Univ, Coll Pharm, Jeonju, South Korea

[5] Kyungpook Natl Univ, Joint Inst Regenerat Med, Daegu, South Korea

来源：

CANCER GENOMICS & PROTEOMICS | 2022年 / 19卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Prostate cancer; SIRT5; metastasis; PI3K/AKT pathway; IL-1B; TRANSCRIPTION; FAMILY; INACTIVATION; METASTASIS; CARCINOMA; INVASION; GROWTH;

D O I：

10.21873/cgp.20303

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aim: Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men globally. Among patients who develop advanced PCa, 80% are affected by bone metastasis, with a sharp drop in survival rate. Despite efforts, the details of mechanisms of metastasis of PCa remain unclear. SIRT5, an NAD(+)-dependent deacylase, is hypothesized to be a crucial regulator of various cancers. The role of SIRT5 in cancer has not been extensively studied compared to other SIRTs. In this study, we showed significantly decreased levels of SIRT5 in PC-3M, a highly aggressive PC-3 cell variant. Materials and Methods: We characterized the differentially expressed proteins between parental and SIRT5 KO PC-3 cells using quantitative proteomics analysis. Results: A significant increase in expression of interleukin-1 beta (IL-1 beta) in SIRT5 KO cells was observed, and the PI3KIAKT/NF-kappa B signaling pathway was found significantly elevated in SIRT5 KO cells by the Gene Ontology annotation and KEGG pathway functional enrichment analysis. Moreover, we confirmed that SIRT5 can bind PI3K by immunoprecipitation analysis. Conclusion: This study is the first to demonstrate a relationship between SIRT5 and PCa metastasis, suggesting that SIRT5-mediated inhibition of the PI3K/AKT/NK-kappa B pathway is reduced for secondary metastasis from bone to other tissues.

引用

页码：50 / 59

页数：10

共 43 条

[41] Sirtuin5 contributes to colorectal carcinogenesis by enhancing glutaminolysis in a deglutarylation-dependent manner [J].