Igf2bp1-KO Mouse

Igf2bp1, the insulin-like growth factor 2 mRNA-binding protein 1, is an oncofetal RNA-binding protein. Its main function is to stabilize target transcripts by protecting them from miRNA-mediated degradation. It is involved in several biological processes and is known to play a role in m6A-dependent regulatory mechanisms [2,3,4,5,6,7,8,9,10]. It can recognize m6A sites in mRNA and is associated with pathways related to cell proliferation, cancer progression, and virus propagation [2,3,4,5,6,7,8,9,10]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially help in further understanding its functions.

In cancer research, Igf2bp1 has been found to be involved in multiple types of cancer. In liver cancer, PRMT3-mediated arginine methylation of Igf2bp1 at R452 promotes oxaliplatin resistance, and PRMT3 overexpression may serve as a biomarker for this resistance [1]. In endometrial cancer, Igf2bp1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner, promoting cancer progression [3]. In breast cancer, USP10 stabilizes Igf2bp1, which then promotes breast cancer metastasis via CPT1A in an m6A-dependent manner [4]. In esophageal squamous cell carcinoma, elevated Igf2bp1 expression enhances the mRNA stability of INHBA, promoting cell invasion and migration [8]. In gastric cancer, TRIM29 enhances antitumor T-cell immunity by promoting Igf2bp1 ubiquitination and subsequent PD-L1 downregulation [7]. In lung cancer, MNX1-AS1 promotes phase separation of Igf2bp1, driving c-Myc-mediated cell-cycle progression and proliferation [9]. In bladder cancer, circFAM13B binds to Igf2bp1, reducing its binding to PKM2 3'UTR, inhibiting glycolysis, and increasing immunotherapy sensitivity [10]. In septic acute kidney injury, induction of Igf2bp1 can induce pyroptosis in renal tubular cells, and inhibiting Igf2bp1 could be a treatment for septic AKI [5]. Additionally, several virus species, including hepatitis B/C, human papillomaviruses, and SARS-CoV-2, recruit Igf2bp1 to promote their propagation, while HIV-1 is inhibited by it [2].

In conclusion, Igf2bp1 is a key regulator in various biological processes, especially in cancer development and virus-host interactions. Studies using KO/CKO mouse models or other loss-of-function experiments could provide more insights into its role in specific diseases. The findings from these model-based studies contribute to our understanding of the molecular mechanisms underlying cancer progression, drug resistance, and virus propagation, potentially offering new therapeutic targets and strategies for these conditions.

References:

1. Shi, Yunxing, Niu, Yi, Yuan, Yichuan, Yuan, Yunfei, Li, Binkui. 2023. PRMT3-mediated arginine methylation of IGF2BP1 promotes oxaliplatin resistance in liver cancer. In Nature communications, 14, 1932. doi:10.1038/s41467-023-37542-5. https://pubmed.ncbi.nlm.nih.gov/37024475/

2. Glaß, Markus, Hüttelmaier, Stefan. 2023. IGF2BP1-An Oncofetal RNA-Binding Protein Fuels Tumor Virus Propagation. In Viruses, 15, . doi:10.3390/v15071431. https://pubmed.ncbi.nlm.nih.gov/37515119/

3. Zhang, Lin, Wan, Yicong, Zhang, Zihan, Cheng, Wenjun, Zhu, Lan. 2021. IGF2BP1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner and promotes endometrial cancer progression. In Theranostics, 11, 1100-1114. doi:10.7150/thno.49345. https://pubmed.ncbi.nlm.nih.gov/33391523/

4. Shi, Jiajun, Zhang, Qianyi, Yin, Xi, Wang, Shouyu, Zhang, Weijie. 2023. Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner. In International journal of biological sciences, 19, 449-464. doi:10.7150/ijbs.76798. https://pubmed.ncbi.nlm.nih.gov/36632454/

5. Mao, Yan, Jiang, Feng, Xu, Xue-Jiao, Juan, Chen-Xia, Zhou, Guo-Ping. 2023. Inhibition of IGF2BP1 attenuates renal injury and inflammation by alleviating m6A modifications and E2F1/MIF pathway. In International journal of biological sciences, 19, 593-609. doi:10.7150/ijbs.78348. https://pubmed.ncbi.nlm.nih.gov/36632449/

6. Liu, Yang, Guo, Qiang, Yang, Heng, Zeng, Ke-Wu, Tu, Peng-Fei. 2022. Allosteric Regulation of IGF2BP1 as a Novel Strategy for the Activation of Tumor Immune Microenvironment. In ACS central science, 8, 1102-1115. doi:10.1021/acscentsci.2c00107. https://pubmed.ncbi.nlm.nih.gov/36032766/

7. Jiang, Tianlu, Xia, Yiwen, Li, Ying, Xu, Zekuan, Wang, Linjun. 2023. TRIM29 promotes antitumor immunity through enhancing IGF2BP1 ubiquitination and subsequent PD-L1 downregulation in gastric cancer. In Cancer letters, 581, 216510. doi:10.1016/j.canlet.2023.216510. https://pubmed.ncbi.nlm.nih.gov/38029830/

8. Wang, Juan-Juan, Chen, Ding-Xiong, Zhang, Yu, Hao, Jia-Jie, Wang, Ming-Rong. 2023. Elevated expression of the RNA-binding protein IGF2BP1 enhances the mRNA stability of INHBA to promote the invasion and migration of esophageal squamous cancer cells. In Experimental hematology & oncology, 12, 75. doi:10.1186/s40164-023-00429-8. https://pubmed.ncbi.nlm.nih.gov/37644505/

9. Zhu, Qingqing, Zhang, Chongguo, Qu, Tianyu, Guo, Renhua, Zhang, Erbao. . MNX1-AS1 Promotes Phase Separation of IGF2BP1 to Drive c-Myc-Mediated Cell-Cycle Progression and Proliferation in Lung Cancer. In Cancer research, 82, 4340-4358. doi:10.1158/0008-5472.CAN-22-1289. https://pubmed.ncbi.nlm.nih.gov/36214649/

10. Lv, Jiancheng, Li, Kai, Yu, Hao, Yang, Xiao, Lu, Qiang. 2023. HNRNPL induced circFAM13B increased bladder cancer immunotherapy sensitivity via inhibiting glycolysis through IGF2BP1/PKM2 pathway. In Journal of experimental & clinical cancer research : CR, 42, 41. doi:10.1186/s13046-023-02614-3. https://pubmed.ncbi.nlm.nih.gov/36747239/