Research Progress on m6A Methylation in Endometrial Cancer
SI Cai-xia
CHENG Yue
SUN Ren-lian
XU Fei-xue
Abstract：Endometrial cancer(EC),as one of the three major malignant tumors in the female reproductive system,shows an increasing trend in incidence and mortality globally.Patients with early-stage EC have a favorable prognosis,but the survival time of those with advanced-stage and recurrent EC is significantly shortened.N6-methyladenosine(m6A)methylation is the most abundant epitranscriptomic modification in eukaryotic RNA,and the metabolism of RNA is dynamically regulated by three types of regulatory factors:methyltransferases,demethylases,and m6A-binding proteins.Studies have shown that abnormal expression of these regulatory factors plays a critical role in the pathogenesis and progression of EC.For instance,methyltransferase like 3(METTL3)activates the protein kinase B(Akt)signaling pathway,and Wilms' tumor 1-associating protein(WTAP)enhances the characteristics of EC stem cells by affecting the early growth response gene 1(EGR1)/PTEN pathway.Fat mass and obesity-associated protein(FTO)and AlkB homolog 5(ALKBH5)promote the proliferation and invasion of EC cells through signaling pathways such as phosphoinositide 3-kinase(PI3K)/Akt and by regulating the expression of insulin-like growth factor 1 receptor(IGF1R),respectively.In addition,YTH m6A RNA-binding protein 2(YTHDF2)and IGF2 mRNA binding protein(IGF2BP)also participate in the regulation of the malignant phenotypes of EC cells.These findings provide novel perspectives for the early diagnosis and precise therapy of EC.In terms of diagnosis and treatment,high expression of proteins such as METTL3,METTL14,and FTO indicates a poor prognosis,while YTHDF2 is a potential biomarker for identifying precancerous lesions.Furthermore,overexpression of METTL3 can activate CD8+T cells to inhibit the proliferation of EC,and the METTL3/FGD5-AS 1 axis mediates paclitaxel resistance,which lays a theoretical foundation for the immunotherapy of EC and the improvement of chemotherapy resistance.
Keywords：MethylationEndometrial neoplasmsTherapyDisease progressionm6A methylationPathogenesis
Publication Date：2025-08-15
Online Publishing Date：2025-09-23(First online date of this platform, not the publication date of the document)
Pages：6( 414-419 )