A Positive Feedback Loop between Inactive VHL-Triggered Histone Lactylation and PDGFRβ Signaling Drives Clear Cell Renal Cell Carcinoma Progression.

ABSTRACT: Inactive von Hippel-Lindau (VHL) is linked to metabolic reprogramming and plays pivotal roles in the pathogenesis of clear cell renal cell carcinoma (ccRCC). Here, we identify a previously unknown oncogenic role for inactive VHL in actively triggering histone lactylation to promote ccRCC progression. In patients with ccRCC, inactive VHL positively correlates with the presence of histone lactylation, and high levels of histone lactylation indicates poor patient prognosis. Inactive VHL-triggered histone lactylation contributes to ccRCC progression by activating the transcription of platelet-derived growth factor receptor β (PDGFRβ). In turn, PDGFRβ signaling is shown to stimulate histone lactylation, thereby forming an oncogenic positive feedback loop in ccRCC. Target correction of aberrant

SUBMITTER: Yang J 

PROVIDER: S-EPMC9134910 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature