LDHA去丁二酰酶Sirtuin 5作为侵袭性癌症癌症转移刺激因子

IF 11.5 2区 生物学 Q1 GENETICS & HEREDITY Genomics, Proteomics & Bioinformatics Pub Date : 2023-02-01 DOI:10.1016/j.gpb.2022.02.004
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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引用次数: 12

摘要

癌症(PCa)是全世界男性最常见的生殖器癌症。大约80%的晚期前列腺癌患者患有骨转移,生存率急剧下降。尽管付出了巨大的努力,但去势抗性前列腺癌(CRPC)的详细机制仍不清楚。Sirtuin 5(SIRT5)是一种NAD+依赖性去琥珀酸酶,被认为是各种癌症的关键调节因子。然而,与其他SIRT相比,SIRT5在癌症中的作用尚未得到广泛研究。在这里,我们揭示了与前列腺癌阶段相比,侵袭性前列腺癌细胞中SIRT5水平显著降低。SIRT5水平下降与患者生存率下降之间的相关性也得到了证实。使用定量全局琥珀酰组分析,我们表征了乳酸脱氢酶a(LDHA)在赖氨酸118(K118su)的琥珀酰化显著增加,其在增加LDH活性中起作用。LDHA-K118su作为SIRT5的底物,显著增加前列腺癌患者前列腺癌细胞的迁移和侵袭以及LDH活性。本研究揭示了SIRT5蛋白表达的减少和LDHA-K118su作为一种参与前列腺癌进展的新机制,可作为预防前列腺癌进展治疗的新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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 desuccinylase, 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.

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来源期刊
Genomics, Proteomics & Bioinformatics
Genomics, Proteomics & Bioinformatics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
14.30
自引率
4.20%
发文量
844
审稿时长
61 days
期刊介绍: Genomics, Proteomics and Bioinformatics (GPB) is the official journal of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China. It aims to disseminate new developments in the field of omics and bioinformatics, publish high-quality discoveries quickly, and promote open access and online publication. GPB welcomes submissions in all areas of life science, biology, and biomedicine, with a focus on large data acquisition, analysis, and curation. Manuscripts covering omics and related bioinformatics topics are particularly encouraged. GPB is indexed/abstracted by PubMed/MEDLINE, PubMed Central, Scopus, BIOSIS Previews, Chemical Abstracts, CSCD, among others.
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