Mir125a-KO Mouse

Mir125a, through its miR125a-5p and miR125a-3p forms, plays diverse regulatory roles. It can target multiple genes and is involved in pathways related to cell differentiation, immune response, and tumorigenesis [1-10]. For example, it is known to target TRAF6, Gab2, and Uvrag among others, influencing processes like T-cell differentiation, glioma invasion, and autophagy regulation [1,2,5].

In a murine model of chronic hemophilic arthropathy (HA), miR125a-5p was significantly downregulated, with elevated expression of its targets STAT1 and TRAF6. Targeted overexpression of miR125a-5p using an Adeno-associated virus vector decreased inflammatory markers and cartilage-degrading matrix metalloproteinases in the joints [3]. In silicosis, knockdown of miR-125a-5p in an animal study regulated T lymphocyte subsets and reduced pulmonary fibrosis by targeting TRAF6 [1]. In K-ras-dependent pulmonary premalignancy, overexpression of miR125a in human bronchial epithelial cells with an activating K-ras mutation reduced production of tumorigenic factors and cell proliferation [4].

In conclusion, Mir125a is a crucial regulator in various biological processes and diseases. Model-based research, especially in murine models, has revealed its role in diseases such as hemophilic arthropathy, silicosis, and pulmonary premalignancy. Understanding Mir125a can provide potential therapeutic targets for these and other related diseases.

References:

1. Ding, Mingcui, Zhang, Chengpeng, Wang, Wei, Hao, Changfu, Yao, Wu. 2023. Silica-exposed macrophages-secreted exosomal miR125a-5p induces Th1/Th2 and Treg/Th17 cell imbalance and promotes fibroblast transdifferentiation. In Ecotoxicology and environmental safety, 267, 115647. doi:10.1016/j.ecoenv.2023.115647. https://pubmed.ncbi.nlm.nih.gov/37918332/

2. Sun, Lei, Zhang, Baogang, Liu, Yuqing, Li, Hongli, Lu, Shijun. 2015. MiR125a-5p acting as a novel Gab2 suppressor inhibits invasion of glioma. In Molecular carcinogenesis, 55, 40-51. doi:10.1002/mc.22256. https://pubmed.ncbi.nlm.nih.gov/25598421/

3. Senthilkumar, Mohankumar B, Sarangi, Pratiksha, Amit, Sonal, Kumar, Narendra, Jayandharan, Giridhara R. 2023. Targeted delivery of miR125a-5p and human Factor VIII attenuates molecular mediators of hemophilic arthropathy. In Thrombosis research, 231, 8-16. doi:10.1016/j.thromres.2023.09.008. https://pubmed.ncbi.nlm.nih.gov/37741049/

4. Liclican, Elvira L, Walser, Tonya C, Hazra, Saswati, Minna, John D, Dubinett, Steven M. 2014. Loss of miR125a expression in a model of K-ras-dependent pulmonary premalignancy. In Cancer prevention research (Philadelphia, Pa.), 7, 845-55. doi:10.1158/1940-6207.CAPR-14-0063. https://pubmed.ncbi.nlm.nih.gov/24913817/

5. Kim, Yunha, Kang, Young-Sook, Lee, Na-Young, Lee, Junghee, Ryu, Hoon. . Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency. In Autophagy, 11, 796-811. doi:10.1080/15548627.2015.1035503. https://pubmed.ncbi.nlm.nih.gov/25946189/