IGF2BP2-modified circular RNA circCHD7 promotes endometrial cancer progression via stabilizing PDGFRB and activating JAK/STAT signaling pathway
Rui Shi, Rong Zhao, Yan Shen, Sitian Wei, Tangansu Zhang, Jun Zhang, Wan Shu, Shuangshuang Cheng, Hua Teng, Hongbo Wang
Abstract
Abstract Circular RNAs (circRNAs) represent a class of covalently closed, single-stranded RNAs and have been linked to cancer progression. N6-methyladenosine (m 6 A) methylation is a ubiquitous RNA modification in cancer cells. Increasing evidence suggests that m 6 A can mediate the effects of circRNAs in cancer biology. In contrast, the post-transcriptional systems of m 6 A and circRNA in the progression of endometrial cancer (EC) remain obscure. The current study identified a novel circRNA with m 6 A modification, hsa_circ_0084582 (circCHD7), which was upregulated in EC tissues. Functionally, circCHD7 was found to promote the proliferation of EC cells. Mechanistically, circCHD7 interacted with insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) to amplify its enrichment. Moreover, circCHD7 increased the mRNA stability of platelet-derived growth factor receptor beta (PDGFRB) in an m 6 A-dependent manner, thereby enhancing its expression. In addition, the circCHD7/IGF2BP2/PDGFRB axis activated the JAK/STAT signaling pathway and promoted EC cell proliferation. In conclusion, these findings provide new insights into the regulation of circRNA-mediated m 6 A modification, and the new “circCHD7-PDGFRB” model of regulation offers new perspectives on circCHD7 as a potential target for EC therapy.