Igf2bp2, also known as Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2/IMP2), is an RNA-binding protein. It functions as an N6-methyladenosine (m6A) reader, enhancing mRNA stability and translation. It is involved in multiple biological processes such as metabolism, cell cycle progression, and is linked to pathways like glutamine metabolism, glycolytic metabolism, and PI3K-Akt signaling pathway. Its dysregulation is associated with various human metabolic diseases and cancers, highlighting its biological importance. Genetic models, especially gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions [2].

In acute myeloid leukemia (AML), high IGF2BP2 expression is associated with poor prognosis. Inhibiting IGF2BP2 with a small-molecule compound shows anti-leukemia effects in vitro and in vivo. IGF2BP2 promotes AML development by regulating genes in the glutamine metabolism pathway in an m6A-dependent manner [1]. In lung adenocarcinoma, IGF2BP2-expressing cell subpopulations promote angiogenesis and metastasis. IGF2BP2 secreted by exosomes from a LUAD cell subpopulation activates endothelial cells by enhancing the RNA stability of FLT4 through m6A modification, activating the PI3K-Akt signaling pathway [3]. In triple-negative breast cancer, IGF2BP2 is highly expressed. It promotes cell cycle progression by recruiting EIF4A1 to enhance the translation initiation of m6A-modified CDK6. Downregulating IGF2BP2 enhances sensitivity to a CDK4/6 inhibitor [4].

In conclusion, Igf2bp2 is a crucial m6A reader involved in mRNA stability and translation, with significant impacts on various biological processes. Through model-based research, especially KO/CKO mouse models, its roles in cancer-related processes like tumor development, angiogenesis, and metastasis have been revealed. These findings suggest that targeting Igf2bp2 could be a potential therapeutic strategy for diseases such as AML, lung adenocarcinoma, and triple-negative breast cancer [1,3,4].

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/