Mir503-KO Mouse

Mir503, associated with the "canonical" miRNA-16 family, is a microRNA with significant biological functions. It plays a role in post-transcriptional regulation of gene expression, influencing processes like cell proliferation, migration, and invasion. Mir503 is involved in multiple pathways, and its dysregulation is linked to various diseases [3].

In a study generating mice with constitutive or conditional deletion of Zswim8 (encoding an essential TDMD factor), deletion of miR-503 rescued the growth of Zswim8-null embryos, directly implicating its role in regulating mammalian body size through the TDMD pathway [2]. In reproductive system cancers, MIR503HG (a lncRNA and host gene for miR-503) transcripts are downregulated, suggesting miR-503 may function as a tumor suppressor in these contexts [1,3]. Additionally, in urogenital cancers, curcumin exerts anticancer effects by upregulating miR-503 [4].

In summary, Mir503 plays crucial roles in regulating mammalian body growth and acts as a potential tumor suppressor in certain cancers. The use of gene knockout (KO) and conditional knockout (CKO) mouse models, such as the Zswim8-related model, has been instrumental in revealing its functions in specific biological processes and disease conditions.

References:

1. Choudhari, Ramesh, Yang, Barbara, Rotwein, Peter, Gadad, Shrikanth S. 2020. Structure and expression of the long noncoding RNA gene MIR503 in humans and non-human primates. In Molecular and cellular endocrinology, 510, 110819. doi:10.1016/j.mce.2020.110819. https://pubmed.ncbi.nlm.nih.gov/32311422/

2. Jones, Benjamin T, Han, Jaeil, Zhang, He, Acharya, Asha, Mendell, Joshua T. 2023. Target-directed microRNA degradation regulates developmental microRNA expression and embryonic growth in mammals. In Genes & development, 37, 661-674. doi:10.1101/gad.350906.123. https://pubmed.ncbi.nlm.nih.gov/37553261/

3. Gupta, Gaurav, Chellappan, Dinesh K, de Jesus Andreoli Pinto, Terezinha, Bebawy, Mary, Dua, Kamal. 2017. Tumor suppressor role of miR-503. In Panminerva medica, 60, 17-24. doi:10.23736/S0031-0808.17.03386-9. https://pubmed.ncbi.nlm.nih.gov/29164842/

4. Mazaheri-Tehrani, Sadegh, Rouzbahani, Shiva, Heidari-Beni, Motahar. 2024. The Association Between Anti-Neoplastic Effects of Curcumin and Urogenital Cancers: A Systematic Review. In BioMed research international, 2024, 9347381. doi:10.1155/2024/9347381. https://pubmed.ncbi.nlm.nih.gov/39445208/