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VHL deficiency augments anthracycline sensitivity of clear cell renal cell carcinomas by down-regulating ALDH2.

ABSTRACT: The von Hippel-Lindau (VHL) is deficient in ?70% of clear-cell renal cell carcinomas (ccRCC), which contributes to the carcinogenesis and drug resistance of ccRCC. Here we show that VHL-deficient ccRCC cells present enhanced cytotoxicity of anthracyclines in a hypoxia-inducible factor-independent manner. By subtractive proteomic analysis coupling with RNAi or overexpression verification, aldehyde dehydrogenase 2 (ALDH2) is found to be transcriptionally regulated by VHL and contributes to enhanced anthracyclines cytotoxicity in ccRCC cells. Furthermore, VHL regulates ALDH2 expression by directly binding the promoter of -130?bp to -160?bp to activate the transcription of hepatocyte nuclear factor 4 alpha (HNF-4?). In addition, a positive correlation is found among the protein expressions of VHL, HNF-4? and ALDH2 in ccRCC samples. These findings will deepen our understanding of VHL function and shed light on precise treatment for ccRCC patients.

SUBMITTER: Gao YH

PROVIDER: S-EPMC5481740 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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VHL deficiency augments anthracycline sensitivity of clear cell renal cell carcinomas by down-regulating ALDH2.

Gao Yao-Hui YH Wu Zhao-Xia ZX Xie Li-Qi LQ Li Cai-Xia CX Mao Yu-Qin YQ Duan Yan-Tao YT Han Bing B Han San-Feng SF Yu Yun Y Lu Hao-Jie HJ Yang Peng-Yuan PY Xu Tian-Rui TR Xia Jing-Lin JL Chen Guo-Qiang GQ Wang Li-Shun LS

Nature communications 20170615

The von Hippel-Lindau (VHL) is deficient in ∼70% of clear-cell renal cell carcinomas (ccRCC), which contributes to the carcinogenesis and drug resistance of ccRCC. Here we show that VHL-deficient ccRCC cells present enhanced cytotoxicity of anthracyclines in a hypoxia-inducible factor-independent manner. By subtractive proteomic analysis coupling with RNAi or overexpression verification, aldehyde dehydrogenase 2 (ALDH2) is found to be transcriptionally regulated by VHL and contributes to enhance ...[more]

PMID: 28643803

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Dataset Information

VHL deficiency augments anthracycline sensitivity of clear cell renal cell carcinomas by down-regulating ALDH2.

Publications

VHL deficiency augments anthracycline sensitivity of clear cell renal cell carcinomas by down-regulating ALDH2.

Similar Datasets

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