PRMT3, a type I protein arginine methyltransferase, is crucial in biology, especially in cancer initiation and development. It catalyzes the mono-methylation and asymmetric di-methylation of histone and non-histone substrates, regulating various cellular functions [5]. It is involved in multiple pathways, such as those related to metabolism, immune response, and signal transduction. Genetic models, like knockout (KO) mouse models, are valuable for studying its functions.

In various cancers, PRMT3 has been shown to play significant roles. In hepatocellular carcinoma (HCC), PRMT3-mediated arginine methylation of IGF2BP1 promotes oxaliplatin resistance, and its overexpression can be a biomarker for this resistance [1]. In endometrial carcinoma, PRMT3-mediated arginine methylation of METTL14 promotes malignant progression and treatment resistance. Inhibition of PRMT3 enhances the susceptibility of EC cells to ferroptosis [2]. In glioblastoma, knockdown of PRMT3 in cell culture and xenograft mouse models reduces cell proliferation, migration, and tumor growth, as it promotes GBM progression by enhancing HIF1A-mediated glycolysis [3]. In HCC, targeting PRMT3 impairs methylation and oligomerization of HSP60, activating cGAS/STING-mediated anti-tumor immunity, and blocking PRMT3 functions synergizes with PD-1 blockade [4]. In invasive micropapillary carcinoma of the breast, overexpression of PRMT3 is an independent risk factor for poor prognosis, and treatment with a PRMT3 inhibitor decreases xenograft tumorigenic capacity [6].

In conclusion, PRMT3 is a key regulator in multiple biological processes and plays important roles in various cancer types. Studies using KO or other loss-of-function models in mice have revealed its contributions to cancer progression, treatment resistance, and immune evasion, providing potential therapeutic targets for these diseases.

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. Wang, Yiru, Wang, Can, Guan, Xue, Chen, Xiuwei, Yin, Hang. 2023. PRMT3-Mediated Arginine Methylation of METTL14 Promotes Malignant Progression and Treatment Resistance in Endometrial Carcinoma. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2303812. doi:10.1002/advs.202303812. https://pubmed.ncbi.nlm.nih.gov/37973560/

3. Liao, Yunfei, Luo, Zaili, Lin, Yifeng, Zhou, Wenhao, Lu, Q Richard. 2022. PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism. In Cell death & disease, 13, 943. doi:10.1038/s41419-022-05389-1. https://pubmed.ncbi.nlm.nih.gov/36351894/

4. Shi, Yunxing, Wu, Zongfeng, Liu, Shaoru, Wang, Guocan, Li, Binkui. 2024. Targeting PRMT3 impairs methylation and oligomerization of HSP60 to boost anti-tumor immunity by activating cGAS/STING signaling. In Nature communications, 15, 7930. doi:10.1038/s41467-024-52170-3. https://pubmed.ncbi.nlm.nih.gov/39256398/

5. Huang, Jiezuo, Qiao, Beining, Yuan, Yixin, Li, Fenghe, Wang, Lei. . PRMT3 and CARM1: Emerging Epigenetic Targets in Cancer. In Journal of cellular and molecular medicine, 29, e70386. doi:10.1111/jcmm.70386. https://pubmed.ncbi.nlm.nih.gov/39964832/

6. Zhi, Renyong, Wu, Kailiang, Zhang, Jingyue, Li, Shuai, Fu, Li. 2023. PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast. In Cancer science, 114, 1912-1928. doi:10.1111/cas.15724. https://pubmed.ncbi.nlm.nih.gov/36637351/