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

Rebecca M. Mello, Diego Gomez Ceballos, Colby R. Sandate, Sicong Wang, Celine Jouffe, Daniel Agudelo, Nina Henriette Uhlenhaut, Nicolas H. Thomä, M. Celeste Simon and Katja A. Lamia ()
Additional contact information
Rebecca M. Mello: Scripps Research Institute
Diego Gomez Ceballos: Scripps Research Institute
Colby R. Sandate: Friedrich Miescher Institute for Biomedical Research
Sicong Wang: Scripps Research Institute
Celine Jouffe: Helmholtz Munich
Daniel Agudelo: Helmholtz Munich
Nina Henriette Uhlenhaut: Helmholtz Munich
Nicolas H. Thomä: Friedrich Miescher Institute for Biomedical Research
M. Celeste Simon: Abramson Family Cancer Research Institute
Katja A. Lamia: Scripps Research Institute

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60904-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60904-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60904-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().