SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis

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,...

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Main Authors: Zhiyu Fang, Qiang Sun, Huihui Yang, Junfang Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.639408/full
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author Zhiyu Fang
Qiang Sun
Huihui Yang
Junfang Zheng
author_facet Zhiyu Fang
Qiang Sun
Huihui Yang
Junfang Zheng
author_sort Zhiyu Fang
collection DOAJ
description 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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spelling doaj.art-bbe8831158e348e1a405177e359edd002022-12-21T22:15:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.639408639408SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting GlycolysisZhiyu Fang0Qiang Sun1Huihui Yang2Junfang Zheng3Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaBlood Purification Center, Beijing Key Laboratory of Pediatric Chronic Kidney Diseases and Blood Purification, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaBeijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaMetabolic 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.639408/fullSDHBrenal cell carcinomaprognosismethylationglycolysis
spellingShingle Zhiyu Fang
Qiang Sun
Huihui Yang
Junfang Zheng
SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis
Frontiers in Oncology
SDHB
renal cell carcinoma
prognosis
methylation
glycolysis
title SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis
title_full SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis
title_fullStr SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis
title_full_unstemmed SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis
title_short SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis
title_sort sdhb suppresses the tumorigenesis and development of ccrcc by inhibiting glycolysis
topic SDHB
renal cell carcinoma
prognosis
methylation
glycolysis
url https://www.frontiersin.org/articles/10.3389/fonc.2021.639408/full
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AT qiangsun sdhbsuppressesthetumorigenesisanddevelopmentofccrccbyinhibitingglycolysis
AT huihuiyang sdhbsuppressesthetumorigenesisanddevelopmentofccrccbyinhibitingglycolysis
AT junfangzheng sdhbsuppressesthetumorigenesisanddevelopmentofccrccbyinhibitingglycolysis