Mir15b-KO Mouse

Mir15b encodes miR-15b-5p, a microRNA located on cytogenetic band 3q25.33. MicroRNAs are critical regulators of apoptosis and proliferation, and Mir15b participates in multiple biological processes and disease-related pathways. It has been implicated in the pathogenesis of various cancers, neurodegenerative diseases, and metabolic disorders [6,3].

In a study on obese adolescents, both high-intensity interval training (HIT) and school-based exercises (SBE) led to a decrease in Mir15b expression, along with improvements in lipid profiles, suggesting its potential link to obesity-related metabolic changes [1]. In colorectal cancer, LINC00473 acts as a tumor suppressor by competitively sponging miR15b-5p, promoting apoptotic protease-activating factor 1 (APAF1) IRES activity, which in turn affects cell proliferation, colony formation, and apoptosis [2]. In clear cell renal cell carcinoma, miR-15b antagomirs enhance sunitinib cytotoxic effects by upregulating PDZK1 levels, indicating its role in drug resistance [4]. Complete loss of miR-15/16 clusters in mice, including Mir15b, promotes hematopoietic progenitor expansion and a myeloid-biased hyperproliferative state, with implications for myeloid neoplasms [5]. Also, miR-15b promotes cardiac ischemia injury by inhibiting the Mitofusin 2/PERK pathway [7].

In conclusion, Mir15b is a key regulator in multiple biological processes and disease conditions. Studies using models such as mouse models with miR-15/16 cluster deletions have revealed its role in cancer, metabolic, and cardiovascular diseases. Understanding Mir15b's functions provides insights into disease mechanisms and potential therapeutic targets for these conditions.

References:

1. Khaliltahmasebi, Rasol, Minasian, Vazgen, Hovsepian, Silva. 2022. Effects of Two Different School-Based Training on Serum miR15b Expression and Lipid Profile of Adolescents with Obesity. In International journal of preventive medicine, 13, 139. doi:10.4103/ijpvm.ijpvm_6_21. https://pubmed.ncbi.nlm.nih.gov/36618534/

2. Wu, Huizhe, Hu, Xiaoyun, Li, Yalun, Zhang, Rui, Wei, Minjie. 2020. LNC473 Regulating APAF1 IRES-Dependent Translation via Competitive Sponging miR574 and miR15b: Implications in Colorectal Cancer. In Molecular therapy. Nucleic acids, 21, 764-779. doi:10.1016/j.omtn.2020.07.009. https://pubmed.ncbi.nlm.nih.gov/32784109/

3. Rezaee, Delsuz, Saadatpour, Fatemeh, Akbari, Nayyereh, Bagheri-Mohammadi, Saeid, Bakhtiari, Mohammad. 2023. The role of microRNAs in the pathophysiology of human central nervous system: A focus on neurodegenerative diseases. In Ageing research reviews, 92, 102090. doi:10.1016/j.arr.2023.102090. https://pubmed.ncbi.nlm.nih.gov/37832609/

4. Wang, Haibo, Zhang, Lijie, Liu, Hua, Bai, Tao, He, Junqi. 2024. PDZK1 confers sensitivity to sunitinib in clear cell renal cell carcinoma by suppressing the PDGFR-β pathway. In British journal of cancer, 131, 347-360. doi:10.1038/s41416-024-02725-4. https://pubmed.ncbi.nlm.nih.gov/38822145/

5. Ng, Anita, Lovat, Francesca, Shih, Andrew J, Croce, Carlo M, Chiorazzi, Nicholas. 2023. Complete miRNA-15/16 loss in mice promotes hematopoietic progenitor expansion and a myeloid-biased hyperproliferative state. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2308658120. doi:10.1073/pnas.2308658120. https://pubmed.ncbi.nlm.nih.gov/37844234/

6. Ghafouri-Fard, Soudeh, Khoshbakht, Tayyebeh, Hussen, Bashdar Mahmud, Taheri, Mohammad, Hajiesmaeili, Mohammadreza. 2022. A Comprehensive Review on Function of miR-15b-5p in Malignant and Non-Malignant Disorders. In Frontiers in oncology, 12, 870996. doi:10.3389/fonc.2022.870996. https://pubmed.ncbi.nlm.nih.gov/35586497/

7. Zhang, Wenhao, Zhang, Mingyu, Ma, Jiao, Xu, Chaoqian, Zhang, Rong. 2024. MicroRNA-15b promotes cardiac ischemia injury by the inhibition of Mitofusin 2/PERK pathway. In Biochemical pharmacology, 226, 116372. doi:10.1016/j.bcp.2024.116372. https://pubmed.ncbi.nlm.nih.gov/38885773/