TRIM14, an interferon-stimulated gene, is a member of the TRIM family involved in ubiquitination modifications. It plays crucial roles in innate immune responses, especially in pathways like cGAS/STING, PI3K/Akt, and NF-κB, and is widely expressed in various tissues [2].

In innate immunity, Trim14-/-mice are highly susceptible to lethal HSV-1 infection as knockout of TRIM14 impairs HSV-1-triggered antiviral responses in a cGAS-dependent manner. TRIM14 inhibits cGAS degradation mediated by p62-dependent selective autophagy, stabilizing cGAS and promoting type I interferon signaling [1]. In cancer, knockdown of TRIM14 in melanoma cells suppressed cell proliferation, migration, invasion, and melanin synthesis, suggesting it may be a target for melanoma treatment. In breast cancer, reducing TRIM14 inhibited cell proliferation and increased apoptosis [3,5]. In chronic inflammatory pain, Trim14 was elevated in the serum of osteoarthritis patients, and its knockdown in rats relieved pain behaviors, indicating it may be a therapeutic target for chronic inflammatory pain [4].

In summary, TRIM14 is essential for innate immune responses, especially in antiviral defense. Gene-knockout models, such as Trim14-/-mice, have revealed its role in various disease conditions including viral infections, cancer, and chronic inflammatory pain, providing potential therapeutic targets for these diseases.

References:

1. Chen, Meixin, Meng, Qingcai, Qin, Yunfei, Wang, Rong-Fu, Cui, Jun. 2016. TRIM14 Inhibits cGAS Degradation Mediated by Selective Autophagy Receptor p62 to Promote Innate Immune Responses. In Molecular cell, 64, 105-119. doi:10.1016/j.molcel.2016.08.025. https://pubmed.ncbi.nlm.nih.gov/27666593/

2. Li, Xinhao, Zhou, Feilong, Niu, Kaiyi, Chen, Tianyi, Zhang, Yewei. 2024. Emerging discoveries on the role of TRIM14: from diseases to immune regulation. In Cell death discovery, 10, 513. doi:10.1038/s41420-024-02276-w. https://pubmed.ncbi.nlm.nih.gov/39719450/

3. Chen, Jiangyan, Huang, Lin, Quan, Jin, Xiang, Debing. 2021. TRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways. In Aging, 13, 13225-13238. doi:10.18632/aging.203003. https://pubmed.ncbi.nlm.nih.gov/33982666/

4. Niu, Zheng, Qu, Shu-Ting, Zhang, Ling, Xu, Zhen-Hua, Zhang, Hai-Long. 2024. Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients. In Neuroscience, 548, 39-49. doi:10.1016/j.neuroscience.2024.04.015. https://pubmed.ncbi.nlm.nih.gov/38697463/

5. Hu, Gaowu, Pen, Wei, Wang, Ming. 2018. TRIM14 Promotes Breast Cancer Cell Proliferation by Inhibiting Apoptosis. In Oncology research, 27, 439-447. doi:10.3727/096504018X15214994641786. https://pubmed.ncbi.nlm.nih.gov/29562956/