PRDM16 suppresses HIF-targeted gene expression in kidney cancer

• DOI: 10.1084/jem.20191005
• Publication Date: 2020-04-06T17:18:56Z
• Authors: Anirban Kundu; Hyeyoung Nam; Sandeep Shelar; Darshan S. Chandr...; Garrett Brinkley; Suman Karki; Tanecia Mitchell; Carolina B. Livi; Phillip Buckhaults; Richard Kirkman; Yawen Tang; Glenn C. Rowe; Shi Wei; Sooryanarayana Va...; Sunil Sudarshan
• Keywords: Kidney cancer; PRDM16

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