LDHA Desuccinylase Sirtuin 5 as A Novel Cancer Metastatic Stimulator in Aggressive Prostate Cancer

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外文摘要：Prostate cancer(PCa)is the most commonly diagnosed genital cancer in men worldwide.Around 80％of the patients who developed advanced PCa suffered from bone metastasis,with a sharp drop in the survival rate.Despite great efforts,the detailed mechanisms underlying castration-resistant PCa(CRPC)remain unclear.Sirtuin 5(SIRT5),an NAD+-dependent desuc-cinylase,is hypothesized to be a key regulator of various cancers.However,compared to other SIRTs,the role of SIRT5 in cancer has not been extensively studied.Here,we revealed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa stages.The correlation between the decrease in the SIRT5 level and the patient's reduced survival rate was also confirmed.Using quantitative global succinylome analysis,we characterized a significant increase in the succinylation at lysine 118(K118su)of lactate dehydrogenase A(LDHA),which plays a role in increasing LDH activity.As a substrate of SIRT5,LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa patients.This study reveals the reduction of SIRT5 protein expression and LDHA-K118su as a novel mechanism involved in PCa progression,which could serve as a new target to prevent CPRC progression for PCa treatment.

外文关键词：

Sirtuin 5Lactate dehydrogenase ALysine succinylationPCa progression

作者：

Oh Kwang Kwon、In Hyuk Bang、So Young Choi、Ju Mi Jeon、Ann-Yae Na、Yan Gao、Sam Seok Cho、Sung Hwan Ki、Youngshik Choe、Jun Nyung Lee、Yun-Sok Ha、Eun Ju Bae、Tae Gyun Kwon、Byung-Hyun Park、Sangkyu Lee

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作者单位：

BK21 Plus KNU Multi-Omics Based Creative Drug Research Team,College of Pharmacy,Research Institute of Pharmaceutical Sciences,Kyungpook National University,Daegu 41566,Republic of Korea

Department of Biochemistry and Molecular Biology,Chonbuk National University Medical School,Jeonju,Jeonbuk 54896,Republic of Korea

College of Pharmacy,Chosun University,Gwangju 61452,Republic of Korea

Korea Brain Research Institute,Daegu 41068,Republic of Korea

Department of Urology,School of Medicine,Kyungpook National University,Daegu 41566,Republic of Korea

Department of Urology,Kyungpook National University Hospital,Daegu 41566,Republic of Korea

College of Pharmacy,Chonbuk University,Jeonju,Jeonbuk 54896,Republic of Korea

School of Pharmacy,Sungkyunkwan University,Suwon 16419,Republic of Korea

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基金：

National Research Foundation of Korea and funded by the Korean GovernmentNational Research Foundation of Korea and funded by the Korean GovernmentNational Research Foundation of Korea and funded by the Korean GovernmentNational Research Foundation of Korea and funded by the Korean GovernmentNational Research Foundation of Korea and funded by the Korean GovernmentKorea Brain Research Institute

项目编号：

MSIPNRF-2018R1D1A1A020435912019R1H1A10798392020M3A9B60378122020R1A2B5B0300234421-BR-02-04

出版年：

2023

DOI：

10.1016/j.gpb.2022.02.004

基因组蛋白质组与生物信息学报(英文版)

中国科学院北京基因组研究所

基因组蛋白质组与生物信息学报(英文版)

CSTPCDCSCD

影响因子：0.495

ISSN：1672-0229

年,卷(期)：2023.21(1)

参考文献量52