YTHDF2 inhibit the tumorigenicity of endometrial cancer via downregulating the expression of IRS1 methylated with m6A

RNA epigenetic modification take part in many biology processes, and the N6-methyladenosine (m⁶A) methylation of specific mRNAs in endometrial Cancer (EC) tissues play a key role in regulating the tumorigenicity of EC, but the specific mechanism still unknown and need to be investigated in the future. Here, we found that m⁶A reader protein YTHDF2 expression was significantly upregulated in EC compare to tumor adjacent tissues, YTHDF2 was then identified to inhibit the proliferation and invasion of EC cell lines. Mechanistically, the m⁶A reader YTHDF2 bind the methylation sites of target transcripts IRS1 and promoted IRS1 mRNA degradation, consequently inhibiting the expression of IRS1 and inhibiting IRS1/Akt signaling pathway, finally inhibit the tumorigenicity of EC. Thus, we demonstrated that YTHDF2 inhibited the proliferation and invasion of EC via inhibiting IRS1 expression in m⁶A epigenetic way, which suggests a potential therapeutic target for EC.