Igf2bp2-KO 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 regulates multiple biological processes, such as mRNA stability and translation, and is involved in various pathways including glutamine metabolism, cell cycle progression, and angiogenesis. It is of great biological importance in human metabolic diseases like diabetes, obesity, and fatty liver, as well as in cancers [2].

In acute myeloid leukemia (AML), high expression of Igf2bp2 is associated with unfavorable prognosis. Inhibition of Igf2bp2 with a small-molecule compound shows anti-leukemia effects in vitro and in vivo. Igf2bp2 promotes AML development and self-renewal of leukemia stem/initiation cells by regulating key targets in the glutamine metabolism pathways in an m6A-dependent manner [1]. In lung adenocarcinoma, Igf2bp2 is preferentially secreted by exosomes in a specific LUAD cell subpopulation, absorbed by an endothelial cell subpopulation, and activates the PI3K-Akt signaling pathway to promote angiogenesis and metastasis, and is linked to poor patient survival [3]. In triple-negative breast cancer (TNBC), Igf2bp2 is highly expressed due to lower promoter methylation. It promotes TNBC proliferation and the G1/S phase transition of the cell cycle by directly regulating CDK6 in an m6A-dependent manner, and down-regulation of Igf2bp2 enhances the sensitivity to abemaciclib, a CDK4/6 inhibitor [4].

In conclusion, Igf2bp2 is a crucial regulator in multiple biological processes. Model-based research, especially in diseases like AML, lung adenocarcinoma, and TNBC, has revealed its oncogenic roles. Inhibiting Igf2bp2 shows potential as a therapeutic strategy in these cancer types, highlighting the importance of Igf2bp2-related research for understanding disease mechanisms and developing novel treatments.

References:

1. Weng, Hengyou, Huang, Feng, Yu, Zhaojin, Huang, Huilin, Chen, Jianjun. 2022. The m6A reader IGF2BP2 regulates glutamine metabolism and represents a therapeutic target in acute myeloid leukemia. In Cancer cell, 40, 1566-1582.e10. doi:10.1016/j.ccell.2022.10.004. https://pubmed.ncbi.nlm.nih.gov/36306790/

2. Wang, Jinyan, Chen, Lijuan, Qiang, Ping. 2021. The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers. In Cancer cell international, 21, 99. doi:10.1186/s12935-021-01799-x. https://pubmed.ncbi.nlm.nih.gov/33568150/

3. Fang, Han, Sun, Qi, Zhou, Jin, Yu, Xiaofeng, Song, Xicheng. 2023. m6A methylation reader IGF2BP2 activates endothelial cells to promote angiogenesis and metastasis of lung adenocarcinoma. In Molecular cancer, 22, 99. doi:10.1186/s12943-023-01791-1. https://pubmed.ncbi.nlm.nih.gov/37353784/

4. Xia, Tian, Dai, Xin-Yuan, Sang, Ming-Yi, Wei, Ji-Fu, Ding, Qiang. 2023. IGF2BP2 Drives Cell Cycle Progression in Triple-Negative Breast Cancer by Recruiting EIF4A1 to Promote the m6A-Modified CDK6 Translation Initiation Process. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2305142. doi:10.1002/advs.202305142. https://pubmed.ncbi.nlm.nih.gov/37983610/