IGF2BPs as novel m6A readers: Diverse roles in regulating cancer cell biological functions, hypoxia adaptation, metabolism, and immunosuppressive tumor microenvironment

Meiqi Duan; Haiyang Liu; Shasha Xu; Zhi Yang; Fusheng Zhang; Guang Wang; Yutian Wang; Shan Zhao; Xiaofeng Jiang

doi:10.1016/j.gendis.2023.06.017

IGF2BPs as novel m⁶A readers: Diverse roles in regulating cancer cell biological functions, hypoxia adaptation, metabolism, and immunosuppressive tumor microenvironment

Genes Dis. 2023 Jul 20;11(2):890-920. doi: 10.1016/j.gendis.2023.06.017. eCollection 2024 Mar.

Authors

Meiqi Duan¹, Haiyang Liu¹, Shasha Xu², Zhi Yang¹, Fusheng Zhang¹, Guang Wang¹, Yutian Wang¹, Shan Zhao³, Xiaofeng Jiang¹

Affiliations

¹ Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China.
² Department of Gastroendoscopy, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China.
³ Department of Rheumatology and Immunology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110002, China.

Abstract

m⁶A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role in cancer progression by regulating biological functions. Insulin-like growth factor 2 mRNA-binding proteins (IGF2BP) are newly identified m⁶A 'readers'. They belong to a family of RNA-binding proteins, which bind to the m⁶A sites on different RNA sequences and stabilize them to promote cancer progression. In this review, we summarize the mechanisms by which different upstream factors regulate IGF2BP in cancer. The current literature analyzed here reveals that the IGF2BP family proteins promote cancer cell proliferation, survival, and chemoresistance, inhibit apoptosis, and are also associated with cancer glycolysis, angiogenesis, and the immune response in the tumor microenvironment. Therefore, with the discovery of their role as 'readers' of m⁶A and the characteristic re-expression of IGF2BPs in cancers, it is important to elucidate their mechanism of action in the immunosuppressive tumor microenvironment. We also describe in detail the regulatory and interaction network of the IGF2BP family in downstream target RNAs and discuss their potential clinical applications as diagnostic and prognostic markers, as well as recent advances in IGF2BP biology and associated therapeutic value.

Keywords: Cancer; IGF2BP; Immunosuppressive TME; Molecular mechanism; Therapy; m6A.

Publication types

Review