Mzf1, also known as zinc finger protein 42, is a zinc finger transcription factor belonging to the Krüppel-like family. It plays crucial roles in multiple biological processes. It is involved in pathways related to cell cycle regulation, apoptosis, and oxidative stress response. Dysregulation of Mzf1 has been associated with various diseases, especially cancers, making it an important target for research [3].

In cancer, Mzf1 has complex roles. In glioblastoma, its high expression promotes cell proliferation, and cantharidin inhibits this by suppressing Mzf1 expression and the Mzf1/c-MYC axis [3]. In hepatocellular carcinoma, Mzf1 promotes tumour progression and resistance to anti-PD-L1 antibody treatment. It binds to the cyclin-dependent kinase 4 (CDK4) activation site, accelerating PD-L1 ubiquitination, and inhibition of CDK4 can restore PD-L1 expression [2]. In non-small cell lung cancer and pancreatic adenocarcinoma, reduced Mzf1 expression in tumours correlates with poor patient survival, and Mzf1 mediates oncogene-induced senescence by promoting p16INK4A transcription [1]. In prostate cancer, Mzf1 positively regulates the CDC37 gene, which is essential for oncogenic signaling pathways, while SCAND1 negatively regulates it [5]. In lung cancer, the UHRF1/DNMT1-Mzf1 axis modulates intragenic site-specific CpGI methylation, regulating the divergent expression of PRSS3 isoforms [6]. In neuroblastoma, MZF1 and MZF1-AS1 are transcriptional regulators of proline synthesis and tumour progression [8]. In addition, in the dorsal root ganglia, Mzf1 contributes to the development and maintenance of neuropathic pain via regulation of TRPV1 [7]. In SH-SY5Y cells, Mzf1 alleviates oxidative stress and apoptosis induced by rotenone by promoting RBM3 transcription [4].

In conclusion, Mzf1 is a key transcription factor with diverse functions. Its dysregulation is closely associated with cancer progression, resistance to immunotherapy, and the development of neuropathic pain. Studies on Mzf1, especially those using in vivo models, have provided insights into its role in disease, offering potential therapeutic targets for various diseases, particularly cancers.

References:

1. Wu, Dan, Tan, Hua, Su, Weijun, Dong, George M, Sun, Peiqing. 2021. MZF1 mediates oncogene-induced senescence by promoting the transcription of p16INK4A. In Oncogene, 41, 414-426. doi:10.1038/s41388-021-02110-y. https://pubmed.ncbi.nlm.nih.gov/34773072/

2. Kan, Anna, Liu, Shuang, He, Minke, Huang, Yexing, Shi, Ming. 2023. MZF1 promotes tumour progression and resistance to anti-PD-L1 antibody treatment in hepatocellular carcinoma. In JHEP reports : innovation in hepatology, 6, 100939. doi:10.1016/j.jhepr.2023.100939. https://pubmed.ncbi.nlm.nih.gov/38074509/

3. Wang, Chie-Hong, Wu, Hsuan-Cheng, Hsu, Chen-Wei, Tseng, Tsui-Hwa, Wang, Shao-Ming. 2022. Inhibition of MZF1/c-MYC Axis by Cantharidin Impairs Cell Proliferation in Glioblastoma. In International journal of molecular sciences, 23, . doi:10.3390/ijms232314727. https://pubmed.ncbi.nlm.nih.gov/36499054/

4. Zhang, Ji, Chai, Wen, Xiang, Zhengbing, Zhou, Xinhua, Zhang, Ping. . MZF1 alleviates oxidative stress and apoptosis induced by rotenone in SH-SY5Y cells by promoting RBM3 transcription. In The Journal of toxicological sciences, 46, 477-486. doi:10.2131/jts.46.477. https://pubmed.ncbi.nlm.nih.gov/34602532/

5. Eguchi, Takanori, Prince, Thomas L, Tran, Manh Tien, Lang, Benjamin J, Calderwood, Stuart K. 2019. MZF1 and SCAND1 Reciprocally Regulate CDC37 Gene Expression in Prostate Cancer. In Cancers, 11, . doi:10.3390/cancers11060792. https://pubmed.ncbi.nlm.nih.gov/31181782/

6. Lin, Shuye, Xu, Hanli, Qin, Lin, Ren, Jianke, Huang, Jiaqiang. 2023. UHRF1/DNMT1-MZF1 axis-modulated intragenic site-specific CpGI methylation confers divergent expression and opposing functions of PRSS3 isoforms in lung cancer. In Acta pharmaceutica Sinica. B, 13, 2086-2106. doi:10.1016/j.apsb.2023.02.015. https://pubmed.ncbi.nlm.nih.gov/37250150/

7. Xing, Fei, Gu, Hanwen, Niu, Qin, Xu, Ji-Tian, Zhang, Wei. 2019. MZF1 in the Dorsal Root Ganglia Contributes to the Development and Maintenance of Neuropathic Pain via Regulation of TRPV1. In Neural plasticity, 2019, 2782417. doi:10.1155/2019/2782417. https://pubmed.ncbi.nlm.nih.gov/31582966/

8. Fang, Erhu, Wang, Xiaojing, Yang, Feng, Zheng, Liduan, Tong, Qiangsong. 2019. Therapeutic Targeting of MZF1-AS1/PARP1/E2F1 Axis Inhibits Proline Synthesis and Neuroblastoma Progression. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 6, 1900581. doi:10.1002/advs.201900581. https://pubmed.ncbi.nlm.nih.gov/31592410/