PRDM16 suppresses HIF-targeted gene expression in kidney cancer

Anirban Kundu, Hyeyoung Nam, Sandeep Shelar, Darshan S. Chandrashekar, Garrett Brinkley, Suman Karki, Tanecia Mitchell, Carolina B. Livi, Phillip Buckhaults, Richard Kirkman, Yawen Tang, Glenn C. Rowe, Shi Wei, Sooryanarayana Varambally, Sunil Sudarshan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Analysis of transcriptomic data demonstrates extensive epigenetic gene silencing of the transcription factor PRDM16 in renal cancer. We show that restoration of PRDM16 in RCC cells suppresses in vivo tumor growth. RNaseq analysis reveals that PRDM16 imparts a predominantly repressive effect on the RCC transcriptome including suppression of the gene encoding semaphorin 5B (SEMA5B). SEMA5B is a HIF target gene highly expressed in RCC that promotes in vivo tumor growth. Functional studies demonstrate that PRDM16’s repressive properties, mediated by physical interaction with the transcriptional corepressors C-terminal binding proteins (CtBP1/2), are required for suppression of both SEMA5B expression and in vivo tumor growth. Finally, we show that reconstitution of RCC cells with a PRDM16 mutant unable to bind CtBPs nullifies PRDM16’s effects on both SEMA5B repression and tumor growth suppression. Collectively, our data uncover a novel epigenetic basis by which HIF target gene expression is amplified in kidney cancer and a new mechanism by which PRDM16 exerts its tumor suppressive effects.

Original languageEnglish (US)
Article numbere20191005
JournalJournal of Experimental Medicine
Issue number6
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Medicine(all)


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