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

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.