4.6 Article

SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis

Journal

FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.639408

Keywords

SDHB; renal cell carcinoma; prognosis; methylation; glycolysis

Categories

Funding

  1. National Natural Science Foundation of the People's Republic of China [81974415, 81600551]
  2. Natural Science Foundation of Beijing [7192021]
  3. Cultivation Fund Project of the National Natural Science Foundation in Beijing Children's Hospital, Capital Medical University [GPMS202002]

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The expression level of SDHB is downregulated in ccRCC tissues, decreasing as the stage and grade progress, and low SDHB level is associated with poor prognosis in ccRCC patients. SDHB suppresses the proliferation and migration of ccRCC cells by inhibiting aerobic 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, 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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