Igf2bp2-flox Mouse

Igf2bp2, also known as insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2/IMP2), is an RNA-binding protein and an N6-methyladenosine (m6A) reader. It plays a crucial role in regulating multiple biological processes. It is involved in post-transcriptional regulation of numerous genes, influencing pathways such as glutamine metabolism, cell cycle progression, angiogenesis, and metastasis. It is of great biological importance as it participates in human metabolic diseases like diabetes, obesity, and fatty liver, as well as in the development and progression of various cancers [2].

In acute myeloid leukemia (AML), high expression of Igf2bp2 is associated with unfavorable prognosis. Knockdown of Igf2bp2 using a small-molecule compound (CWI1-2) shows anti-leukemia effects both in vitro and in vivo. Igf2bp2 promotes AML development and self-renewal of leukemia stem/initiation cells by regulating critical targets in the glutamine metabolism pathways in an m6A-dependent manner [1].

In lung adenocarcinoma, Igf2bp2 is specifically expressed in certain cell subpopulations. Its knockdown may potentially inhibit angiogenesis and metastasis, as it activates endothelial cells to promote these processes through an m6A-mediated mechanism [3].

In triple-negative breast cancer (TNBC), Igf2bp2 is highly expressed. Downregulation of Igf2bp2 in TNBC cells enhances their sensitivity to abemaciclib, a CDK4/6 inhibitor. Igf2bp2 promotes TNBC proliferation and cell cycle transition via directly regulating CDK6 in an m6A-dependent manner [4].

In conclusion, Igf2bp2, as an m6A reader, is involved in multiple biological processes and diseases. Through gene-knockout or knockdown models in various disease settings such as AML, lung adenocarcinoma, and TNBC, its role in promoting disease progression has been revealed. These findings suggest that targeting Igf2bp2 could be a promising therapeutic strategy for these diseases.