Fhl1, the four-and-a-half-LIM domain protein 1, has diverse functions. It is involved in multiple biological processes and is associated with various signaling pathways. Genetic models, especially knockout mouse models, are valuable for studying its functions. It has been linked to different disease conditions, highlighting its overall biological importance [1-3].

In gene knockout studies, FHL1-/-mice infected with chikungunya virus (CHIKV) or o'nyong-nyong virus (ONNV) showed reduced arthritis, myositis, immune infiltrates, and pro-inflammatory cytokine/chemokine outputs compared to wild-type mice [1]. This indicates that FHL1 promotes CHIKV and ONNV infection and pathogenesis. In glioblastoma, FHL1 overexpression promotes cell growth, migration, and invasion both in vivo and in vitro, while its silencing has the opposite effects, suggesting its role in promoting tumor malignancy [2]. In acute myeloid leukemia (AML), knockdown of FHL1 inhibited cell proliferation, induced cell cycle arrest, and promoted cell differentiation, and in vivo depletion of FHL1 inhibited tumor growth [3].

In conclusion, Fhl1 is involved in multiple biological processes and disease conditions. Gene knockout mouse models have been crucial in revealing its role in viral infections like those caused by CHIKV and ONNV, as well as in cancers such as glioblastoma and AML. These studies provide insights into potential therapeutic targets related to Fhl1-associated diseases.

References:

1. Ng, Wern Hann, Liu, Xiang, Ling, Zheng L, King, Nicholas J C, Mahalingam, Suresh. 2023. FHL1 promotes chikungunya and o'nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design. In Nature communications, 14, 6605. doi:10.1038/s41467-023-42330-2. https://pubmed.ncbi.nlm.nih.gov/37884534/

2. Sun, Lili, Chen, Lili, Zhu, Hua, Chen, Clark C, Li, Ming. 2020. FHL1 promotes glioblastoma aggressiveness through regulating EGFR expression. In FEBS letters, 595, 85-98. doi:10.1002/1873-3468.13955. https://pubmed.ncbi.nlm.nih.gov/33053208/

3. Liu, Yabo, Li, Huibo, Zhao, Yanqiu, Fu, Jinyue, Fan, Shengjin. 2022. Targeting FHL1 impairs cell proliferation and differentiation of acute myeloid leukemia cells. In Biochemistry and cell biology = Biochimie et biologie cellulaire, 100, 301-308. doi:10.1139/bcb-2021-0507. https://pubmed.ncbi.nlm.nih.gov/35916339/