IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms15337.html
   My bibliography  Save this article

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

Author

Listed:
  • Yao-Hui Gao

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • Zhao-Xia Wu

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • Li-Qi Xie

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • Cai-Xia Li

    (Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Ruijin Hospital, Shanghai Jiaotong University School of Medicine)

  • Yu-Qin Mao

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • Yan-Tao Duan

    (Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Ruijin Hospital, Shanghai Jiaotong University School of Medicine)

  • Bing Han

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • San-Feng Han

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • Yun Yu

    (Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Ruijin Hospital, Shanghai Jiaotong University School of Medicine)

  • Hao-Jie Lu

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • Peng-Yuan Yang

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • Tian-Rui Xu

    (Faculty of Life Science and Technology, Kunming University of Science and Technology)

  • Jing-Lin Xia

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University)

  • Guo-Qiang Chen

    (Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Ruijin Hospital, Shanghai Jiaotong University School of Medicine)

  • Li-Shun Wang

    (Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University
    Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Ruijin Hospital, Shanghai Jiaotong University School of Medicine)

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-4α). In addition, a positive correlation is found among the protein expressions of VHL, HNF-4α and ALDH2 in ccRCC samples. These findings will deepen our understanding of VHL function and shed light on precise treatment for ccRCC patients.

Suggested Citation

  • Yao-Hui Gao & Zhao-Xia Wu & Li-Qi Xie & Cai-Xia Li & Yu-Qin Mao & Yan-Tao Duan & Bing Han & San-Feng Han & Yun Yu & Hao-Jie Lu & Peng-Yuan Yang & Tian-Rui Xu & Jing-Lin Xia & Guo-Qiang Chen & Li-Shun , 2017. "VHL deficiency augments anthracycline sensitivity of clear cell renal cell carcinomas by down-regulating ALDH2," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15337
    DOI: 10.1038/ncomms15337
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms15337
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms15337?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15337. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.