SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis.
SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis.
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DOI：
10.3389/fonc.2021.639408
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Fang Z;Sun Q;Yang H;Zheng J
代谢重编程是肾透明细胞癌（ccRCC）的显著特征。琥珀酸脱氢酶亚基B（SDHB）是线粒体呼吸链复合体II的亚基之一。SDHB功能的丧失与肾癌细胞的代谢变化密切相关。但SDHB在ccRCC发生发展中的作用及分子机制尚不清楚。在本研究中，GEO，TCGA和oncomine数据库的生物信息学分析和免疫组织化学的结果表明，SDHB在ccRCC组织中的表达水平下调。SDHB水平随着ccRCC分期和分级的进展而逐渐下调。低水平的SDHB与ccRCC患者的不良预后相关，特别是对于晚期ccRCC患者。SDHB基因启动子区甲基化水平升高导致ccRCC组织中SDHB水平下调。SDHB与多种代谢相关基因相关，其相互作用蛋白在代谢途径中富集。SDHB过表达通过抑制有氧糖酵解抑制ccRCC细胞的增殖、集落形成和迁移。SDHB可能是ccRCC的潜在预后标志物和治疗靶点。
Metabolic reprogramming is the prominent feature of clear cell renal cell carcinoma (ccRCC). Succinate dehydrogenase subunit B (SDHB) is one of subunits of mitochondrial respiratory chain complex II. The loss of SDHB function is closely related with metabolic changes in kidney cancer cells. However, the role and molecular mechanism of SDHB in ccRCC occurrence and progression are still unclear. In this study, the results of bioinformatics analyses on GEO, TCGA and oncomine databases and immunohistochemistry showed that the expression level of SDHB was downregulated in ccRCC tissues. SDHB level was gradually downregulated as ccRCC stage and grade progressed. The low level of SDHB was associated with poor prognosis of ccRCC patients, especially for advanced ccRCC patients. Increased methylation levels in SDHB gene promoter led to the downregulation of SDHB level in ccRCC tissues. SDHB was correlated with many metabolism related genes and its interacting proteins were enriched in metabolic pathways. SDHB overexpression suppressed the proliferation, colony formation and migration of ccRCC cells by inhibiting aerobic glycolysis. SDHB may be a potential prognostic marker and therapeutic target for ccRCC.
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DOI：
10.1038/nrurol.2010.47
发表时间：
2010-05
期刊：
Nature reviews. Urology
影响因子：
--
作者：
通讯作者：
--
影响因子：
13.8
作者：
Liberti MV;Locasale JW
通讯作者：
Locasale JW
影响因子：
5.6
作者：
Ata R;Antonescu CN
通讯作者：
Antonescu CN
影响因子：
--
作者：
Muglia VF;Prando A
通讯作者：
Prando A
影响因子：
3
作者：
Miranda-Goncalves, Vera;Reis, Rui M.;Baltazar, Fatima
通讯作者：
Baltazar, Fatima