IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-60904-0.html
   My bibliography  Save this article

BMAL1 and ARNT enable circadian HIF2α responses in clear cell renal cell carcinoma

Author

Listed:
  • Rebecca M. Mello

    (Scripps Research Institute
    Scripps Research Institute)

  • Diego Gomez Ceballos

    (Scripps Research Institute
    Scripps Research Institute)

  • Colby R. Sandate

    (Friedrich Miescher Institute for Biomedical Research)

  • Sicong Wang

    (Scripps Research Institute
    Scripps Research Institute)

  • Celine Jouffe

    (Helmholtz Munich
    Helmholtz Munich)

  • Daniel Agudelo

    (Helmholtz Munich)

  • Nina Henriette Uhlenhaut

    (Helmholtz Munich
    TUM School of Life Sciences & ZIEL Institute for Food and Health)

  • Nicolas H. Thomä

    (Friedrich Miescher Institute for Biomedical Research)

  • M. Celeste Simon

    (Abramson Family Cancer Research Institute
    University of Pennsylvania)

  • Katja A. Lamia

    (Scripps Research Institute
    Scripps Research Institute)

Abstract

Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). The core circadian transcription factor BMAL1 is closely related to ARNT, and we show that BMAL1-HIF2α regulates a subset of HIF2α target genes in ccRCC cells. Depletion of BMAL1 selectively reduces HIF2α chromatin association and target gene expression and reduces ccRCC growth in culture and in xenografts. Analysis of pre-existing data reveals higher BMAL1 in patient-derived xenografts that are sensitive to growth suppression by a HIF2α antagonist (PT2399). BMAL1-HIF2α is more sensitive than ARNT-HIF2α is to suppression by PT2399, and the effectiveness of PT2399 for suppressing xenograft tumor growth in vivo depends on the time of day at which it is delivered. Together, these findings indicate that an alternate HIF2α heterodimer containing the circadian partner BMAL1 influences HIF2α activity, growth, and sensitivity to HIF2α antagonist drugs in ccRCC cells.

Suggested Citation

  • Rebecca M. Mello & Diego Gomez Ceballos & Colby R. Sandate & Sicong Wang & Celine Jouffe & Daniel Agudelo & Nina Henriette Uhlenhaut & Nicolas H. Thomä & M. Celeste Simon & Katja A. Lamia, 2025. "BMAL1 and ARNT enable circadian HIF2α responses in clear cell renal cell carcinoma," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60904-0
    DOI: 10.1038/s41467-025-60904-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-60904-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-60904-0?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:16:y:2025:i:1:d:10.1038_s41467-025-60904-0. 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.