The m <sup>6</sup> A RNA demethylase FTO is a HIF-independent synthetic lethal partner with the VHL tumor suppressor
Yiren Xiao, Kaushik N. Thakkar, Hongjuan Zhao, James P. Broughton, Yang Li, José A. Seoane, Anh N. Diep, Thomas J. Metzner, Rie von Eyben, David L. Dill, James D. Brooks, Christina Curtis, John T. Leppert, Jiangbin Ye, Donna M. Peehl, Amato J. Giaccia, Subarna Sinha, Erinn B. Rankin
Abstract
Significance Here we report a synthetic lethal interaction between the epitranscriptomic modifier FTO and the tumor suppressor VHL. Notably, FTO inhibition reduced the growth of both HIF wild type and HIF-deficient tumors. These findings reveal an epitranscriptomic vulnerability of VHL-deficient cells and identify a potential HIF-independent therapeutic target for ccRCC tumors.
Topics & Concepts
SuppressorDemethylaseRNACancer researchChemistryMolecular biologyBiologyGeneBiochemistryEpigeneticsRNA modifications and cancerCancer-related gene regulationCancer-related molecular mechanisms research