The m⁶A RNA demethylase FTO is a HIF-independent synthetic lethal partner with the VHL tumor suppressor.

ABSTRACT: Loss of the von Hippel-Lindau (VHL) tumor suppressor is a hallmark feature of renal clear cell carcinoma. VHL inactivation results in the constitutive activation of the hypoxia-inducible factors (HIFs) HIF-1 and HIF-2 and their downstream targets, including the proangiogenic factors VEGF and PDGF. However, antiangiogenic agents and HIF-2 inhibitors have limited efficacy in cancer therapy due to the development of resistance. Here we employed an innovative computational platform, Mining of Synthetic Lethals (MiSL), to identify synthetic lethal interactions with the loss of VHL through analysis of primary tumor genomic and transcriptomic data. Using this approach, we identified a synthetic lethal interaction between VHL and the m⁶A RNA demethylase FTO in renal cell carcinoma. MiSL

SUBMITTER: Xiao Y 

PROVIDER: S-EPMC7474618 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature