FTO-Dependent N ⁶-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling.

ABSTRACT: N ⁶-Methyladenosine (m⁶A) is the most abundant modification of mammalian mRNAs. RNA methylation fine tunes RNA stability and translation, altering cell fate. The fat mass- and obesity-associated protein (FTO) is an m⁶A demethylase with oncogenic properties in leukemia. Here, we show that FTO expression is suppressed in ovarian tumors and cancer stem cells (CSC). FTO inhibited the self-renewal of ovarian CSC and suppressed tumorigenesis in vivo, both of which required FTO demethylase activity. Integrative RNA sequencing and m⁶A mapping analysis revealed significant transcriptomic changes associated with FTO overexpression and m⁶A loss involving stem cell signaling, RNA transcription, and mRNA splicing pathway

SUBMITTER: Huang H 

PROVIDER: S-EPMC7442742 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature