Genome-wide CRISPR screen identifies a cytokine-enhancer circuit driving HIF-2α activation in renal cancer - PubMed
4 hours ago
- #Renal Cancer
- #CRISPR
- #HIF-2α
- Genome-wide CRISPR screen identifies SOCS3 as a key negative regulator of HIF-2α in ccRCC.
- Loss of SOCS3 activates JAK1-STAT3 signaling, leading to STAT3 recruitment to EPAS1 enhancers, driving HIF-2α transcription.
- The cytokine-enhancer circuit is validated in ccRCC patient samples and through CRISPR interference, reducing tumor growth.
- SOCS3 overexpression or JAK1/STAT3 inhibition suppresses HIF-2α expression and tumor progression in vitro and in vivo.
- Findings suggest combined JAK1/STAT3 and HIF-2α inhibition may overcome therapeutic resistance in kidney cancer.