MYH9, encoding the heavy chain of non-muscle myosin IIA, is a cytoplasmic myosin involved in generating intracellular chemomechanical force and actin cytoskeleton translocation. Its functions are regulated by phosphorylation of light and heavy chains and protein-protein interactions. It plays a role in various biological processes, especially during embryonic development, and is associated with pathways related to cell motility and tissue homeostasis [1].

MYH9-related diseases are caused by its mutations, following an autosomal-dominant pattern. These diseases include a group of rare genetic entities characterized by macrothrombocytopenia, leukocyte inclusions, and risks of renal failure, hearing loss, and cataracts [2]. In hepatocellular carcinoma, silencing MYH9 blocks HBx-induced GSK3β ubiquitination and degradation, inhibiting tumor stemness [3]. In gastric cancer, nuclear MYH9 promotes CTNNB1 transcription, leading to anoikis resistance and metastasis [4]. In rheumatoid arthritis, MYH9 promotes synoviocyte migration and invasion [5]. MYH9-related platelet disorders are due to MYH9 gene mutations causing premature platelet release, macrothrombocytopenia, and cytoplasmic inclusion bodies in leukocytes [6]. In serous ovarian cancer, MYH9 combines with MYH10 to promote carcinogenesis, progression, and cisplatin resistance [7]. Also, OVGP1 promotes hypertension by interacting with MYH9, inducing vascular remodeling [8].

In conclusion, MYH9 is crucial for intracellular force-generation and cytoskeleton-related processes. Model-based research, especially through gene-knockout studies in relevant animal models, has revealed its diverse roles in multiple disease areas, including blood disorders, cancers, and cardiovascular diseases. Understanding MYH9's functions provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Pecci, Alessandro, Ma, Xuefei, Savoia, Anna, Adelstein, Robert S. 2018. MYH9: Structure, functions and role of non-muscle myosin IIA in human disease. In Gene, 664, 152-167. doi:10.1016/j.gene.2018.04.048. https://pubmed.ncbi.nlm.nih.gov/29679756/

2. Furlano, Mónica, Arlandis, Rosa, Venegas, María Del Prado, Ars, Elisabet, Torra, Roser. 2018. MYH9 Associated nephropathy. In Nefrologia, 39, 133-140. doi:10.1016/j.nefro.2018.08.008. https://pubmed.ncbi.nlm.nih.gov/30471777/

3. Lin, Xian, Li, Ai-Min, Li, Yong-Hao, Liu, Zhen, Fang, Wei-Yi. 2020. Silencing MYH9 blocks HBx-induced GSK3β ubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma. In Signal transduction and targeted therapy, 5, 13. doi:10.1038/s41392-020-0111-4. https://pubmed.ncbi.nlm.nih.gov/32296025/

4. Ye, Gengtai, Yang, Qingbin, Lei, Xuetao, Yu, Jiang, Li, Guoxin. 2020. Nuclear MYH9-induced CTNNB1 transcription, targeted by staurosporin, promotes gastric cancer cell anoikis resistance and metastasis. In Theranostics, 10, 7545-7560. doi:10.7150/thno.46001. https://pubmed.ncbi.nlm.nih.gov/32685004/

5. Lee, Saseong, Choi, Eunbyeol, Chae, Sehyun, Hwang, Daehee, Kim, Wan-Uk. 2023. Identification of MYH9 as a key regulator for synoviocyte migration and invasion through secretome profiling. In Annals of the rheumatic diseases, 82, 1035-1048. doi:10.1136/ard-2022-223625. https://pubmed.ncbi.nlm.nih.gov/37188496/

6. Althaus, Karina, Greinacher, Andreas. 2009. MYH9-related platelet disorders. In Seminars in thrombosis and hemostasis, 35, 189-203. doi:10.1055/s-0029-1220327. https://pubmed.ncbi.nlm.nih.gov/19408192/

7. Liu, Longyang, Chen, Chunlin, Liu, Ping, Zeng, Zhaoyang, Fang, Weiyi. 2023. MYH10 Combines with MYH9 to Recruit USP45 by Deubiquitinating Snail and Promotes Serous Ovarian Cancer Carcinogenesis, Progression, and Cisplatin Resistance. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2203423. doi:10.1002/advs.202203423. https://pubmed.ncbi.nlm.nih.gov/36929633/

8. Bai, Congxia, Su, Ming, Zhang, Yaohua, Li, Hao, Chen, Jingzhou. 2022. Oviductal Glycoprotein 1 Promotes Hypertension by Inducing Vascular Remodeling Through an Interaction With MYH9. In Circulation, 146, 1367-1382. doi:10.1161/CIRCULATIONAHA.121.057178. https://pubmed.ncbi.nlm.nih.gov/36172862/