YTHDF2 inhibit the tumorigenicity of endometrial cancer via downregulating the expression of IRS1 methylated with m<sup>6</sup>A
Ling Hong, Xiaowen Pu, Haili Gan, Lichun Weng, Qingliang Zheng
Abstract
RNA epigenetic modification take part in many biology processes, and the N6-methyladenosine (m 6 A) 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 m 6 A 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 m 6 A 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 m 6 A epigenetic way, which suggests a potential therapeutic target for EC.