IGF2BP2-modified circular RNA circCHD7 promotes endometrial cancer progression via stabilizing PDGFRB and activating JAK/STAT signaling pathway

  • Cancer Gene Ther. 2024 May 22. doi: 10.1038/s41417-024-00781-9.
Rui Shi  1 ,  Rong Zhao  1 ,  Yan Shen  2 ,  Sitian Wei  1 ,  Tangansu Zhang  1 ,  Jun Zhang  1 ,  Wan Shu  1 ,  Shuangshuang Cheng  1 ,  Hua Teng  1 ,  Hongbo Wang  3
Affiliations
  • 1. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR China.
  • 2. Health Management Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR China.
  • 3. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR China. [email protected].
PMID: 38778089 DOI: 10.1038/s41417-024-00781-9
Abstract

Circular RNAs (circRNAs) represent a class of covalently closed, single-stranded RNAs and have been linked to Cancer progression. N6-methyladenosine (m6A) methylation is a ubiquitous RNA modification in Cancer cells. Increasing evidence suggests that m6A can mediate the effects of circRNAs in Cancer biology. In contrast, the post-transcriptional systems of m6A and circRNA in the progression of Endometrial Cancer (EC) remain obscure. The current study identified a novel circRNA with m6A 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 m6A-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 m6A modification, and the new "circCHD7-PDGFRB" model of regulation offers new perspectives on circCHD7 as a potential target for EC therapy.

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