Interferon-induced protein 44-like (IFI44L) is an immune-related gene and a member of interferon-stimulated genes (ISGs). It participates in network transduction, epigenetic modifications, apoptosis, cell-matrix formation, and other pathways, playing a crucial role in tumors, autoimmune diseases, and viral infections [1].

IFI44L expression is induced by IFN and HIV-1 infection, and is regulated by IRF-1 through binding to one of its IFN-stimulated response elements (ISREs) [2]. In lung carcinogenesis, IFI44L acts as a tumor suppressor, promoting apoptosis via the JAK/STAT1 pathway [3]. In tuberculosis, it serves as an antimicrobial target and positive modulator in human macrophages, restricting Mycobacterium tuberculosis intracellular survival [4]. In proliferative diabetic retinopathy, IFI44L may be a biomarker, potentially affecting disease progression by regulating metabolism-related and inflammatory pathways [5]. In systemic lupus erythematosus, it may play a role through abnormal regulation of the type I interferon signalling pathway, and its overexpression in monocytes enhances the maturation and functions of monocyte-derived dendritic cells [6,9]. Variant forms of the IFI44L gene are protective against early-childhood respiratory tract infections or acute otitis media, attenuating IFN pathway activation by respiratory viruses [8]. In head and neck squamous cell carcinoma, ACSL4 upregulates IFI44L expression, promoting cell proliferation and invasiveness [7].

In summary, IFI44L is significantly involved in multiple biological processes and disease conditions, such as cancer, autoimmune diseases, and infections. Its role in these areas has been revealed through various functional studies, which may provide new perspectives for understanding disease mechanisms and developing potential therapeutic strategies.

References:

1. Du, Juan, Luo, Hui, Ye, Shuang, Zheng, Zhen, Liu, Kaitai. 2024. Unraveling IFI44L's biofunction in human disease. In Frontiers in oncology, 14, 1436576. doi:10.3389/fonc.2024.1436576. https://pubmed.ncbi.nlm.nih.gov/39737399/

2. Li, Yutong, Zhang, Junshi, Wang, Chenchen, Li, Yue, Tan, Juan. 2020. IFI44L expression is regulated by IRF-1 and HIV-1. In FEBS open bio, 11, 105-113. doi:10.1002/2211-5463.13030. https://pubmed.ncbi.nlm.nih.gov/33159419/

3. Zeng, Yong, Chen, Hong-Qiang, Zhang, Zhe, Zhou, Zi-Yuan, Liu, Wen-Bin. 2022. IFI44L as a novel epigenetic silencing tumor suppressor promotes apoptosis through JAK/STAT1 pathway during lung carcinogenesis. In Environmental pollution (Barking, Essex : 1987), 319, 120943. doi:10.1016/j.envpol.2022.120943. https://pubmed.ncbi.nlm.nih.gov/36584854/

4. Jiang, Haiqin, Tsang, Lemuel, Wang, Hongsheng, Liu, Changhong. 2021. IFI44L as a Forward Regulator Enhancing Host Antituberculosis Responses. In Journal of immunology research, 2021, 5599408. doi:10.1155/2021/5599408. https://pubmed.ncbi.nlm.nih.gov/34722780/

5. Shang, Mingxin, Zhang, Yao, Zhang, Tongtong. . IFI44L and C1QTNF5 as promising biomarkers of proliferative diabetic retinopathy. In Medicine, 101, e31961. doi:10.1097/MD.0000000000031961. https://pubmed.ncbi.nlm.nih.gov/36451477/

6. Wang, Yuan, Jia, Wei, Ma, Qian, Huo, Zhenghao, Dang, Jie. 2022. Identification of IFI44L as a new candidate molecular marker for systemic lupus erythematosus. In Clinical and experimental rheumatology, 41, 48-59. doi:10.55563/clinexprheumatol/q3aa6s. https://pubmed.ncbi.nlm.nih.gov/35349411/

7. Rupa, Darius, Chuang, Hao-Wen, Hu, Chung-En, Lee, Herng-Sheng, Yuan, Ta-Chun. 2024. ACSL4 upregulates IFI44 and IFI44L expression and promotes the proliferation and invasiveness of head and neck squamous cell carcinoma cells. In Cancer science, 115, 3026-3040. doi:10.1111/cas.16236. https://pubmed.ncbi.nlm.nih.gov/38989827/

8. Lempainen, Johanna, Korhonen, Laura S, Kantojärvi, Katri, Paunio, Tiina, Peltola, Ville. . Associations Between IFI44L Gene Variants and Rates of Respiratory Tract Infections During Early Childhood. In The Journal of infectious diseases, 223, 157-165. doi:10.1093/infdis/jiaa341. https://pubmed.ncbi.nlm.nih.gov/32561935/

9. Luo, Shuaihantian, Wu, Ruifang, Li, Qianwen, Zhang, Guiying. 2022. Epigenetic Regulation of IFI44L Expression in Monocytes Affects the Functions of Monocyte-Derived Dendritic Cells in Systemic Lupus Erythematosus. In Journal of immunology research, 2022, 4053038. doi:10.1155/2022/4053038. https://pubmed.ncbi.nlm.nih.gov/35592687/