Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is one of the components of m6A binding proteins. It plays a crucial role in decoding m6A marks on RNA, thus participating in multiple biological activities such as localization, stability, and immunity of RNAs [2]. It is involved in various biological processes and is associated with many diseases, especially cancers.

In breast cancer, the METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating m6A modification of PD-L1 mRNA, promoting PD-L1 mRNA stabilization and subsequent tumor immune escape [1]. In non-small cell lung cancer, IGF2BP3 upregulation leads to acquired resistance to EGFR tyrosine kinase inhibitors. It promotes oxidative phosphorylation via the IGF2BP3-COX6B2 axis, where IGF2BP3 binds to the 3'-untranslated region of COX6B2 in an m6A-dependent manner to increase its mRNA stability [3]. In cervical cancer, IGF2BP3 enhances lipid metabolism by upregulating SCD expression through regulating SCD mRNA m6A modifications via the IGF2BP3-METTL14 complex, promoting cancer cell proliferation and metastasis [4].

In summary, IGF2BP3 is a key factor in multiple biological processes, especially in the context of cancer. Its role in promoting tumorigenesis and drug resistance in various cancers, as revealed by functional studies in relevant models, highlights its potential as a therapeutic target and prognostic marker. Understanding IGF2BP3 function through gene knockout or conditional knockout mouse models could provide new strategies for treating related diseases.

References:

1. Wan, Weijun, Ao, Xiang, Chen, Quan, Luo, Donglin, Xu, Xiang. 2022. METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N6-methyladenosine modification of PD-L1 mRNA in breast cancer. In Molecular cancer, 21, 60. doi:10.1186/s12943-021-01447-y. https://pubmed.ncbi.nlm.nih.gov/35197058/

2. Liu, Xin, Chen, Jiayu, Chen, Wenliang, Shen, Yang, Xu, Ximing. 2023. Targeting IGF2BP3 in Cancer. In International journal of molecular sciences, 24, . doi:10.3390/ijms24119423. https://pubmed.ncbi.nlm.nih.gov/37298373/

3. Lin, Ziyou, Li, Jingwei, Zhang, Jian, Liu, Peiqing, Zhang, Xiaolei. . Metabolic Reprogramming Driven by IGF2BP3 Promotes Acquired Resistance to EGFR Inhibitors in Non-Small Cell Lung Cancer. In Cancer research, 83, 2187-2207. doi:10.1158/0008-5472.CAN-22-3059. https://pubmed.ncbi.nlm.nih.gov/37061993/

4. Han, Chenying, Hu, Chenchen, Liu, Tianyue, Yang, Kun, Yang, Shuya. 2024. IGF2BP3 enhances lipid metabolism in cervical cancer by upregulating the expression of SCD. In Cell death & disease, 15, 138. doi:10.1038/s41419-024-06520-0. https://pubmed.ncbi.nlm.nih.gov/38355626/