Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.

ABSTRACT: High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PH

SUBMITTER: Wu XN 

PROVIDER: S-EPMC10786316 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature