N6-methyladenosine (m6A), the most abundant internal modification on mRNAs in eukaryotes, plays a role in endometriosis (EMs). However, the underlying mechanism remains largely unclear. Here, we found that FTO is downregulated in EMs; and plays an important role in regulating glycolysis, proliferation, and metastasis of ectopic endometriotic stromal cells (EESCs) by targeting ATG5. We demonstrated that FTO promotes ATG5 expression in a m6A-dependent manner, and further studies revealed that PKM2 is a target of ATG5. Upon FTO overexpression, increased ATG5 protein expression at low m6A levels inhibited the expression of PKM2, thereby reducing the glycolysis level of EESCs. In addition, we demonstrated through in vitro functional experiments that FTO regulates glycolysis, proliferation, and metastasis of EESCs through the ATG5/PKM2 axis. In conclusion, these findings reveal the functional importance of the m6A methylation mechanism of FTO in regulating the development of EMs, which expands our understanding of this interaction, which is crucial for the development of therapeutic strategies for EMs.
Keywords: Autophagy; Endometriosis; FTO; Glycolysis; m6A methylation.
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