MYH9 in Genetic Disorders and Cancer: Potential as a Therapeutic Target and Remaining Challenges
MYH9 and NMIIA in cell movement
MYH9 is a gene involved in cell migration, division, and signaling, and is also studied in genetic disorders and various cancers. This review, published in the international journal Genes & Diseases, summarizes MYH9 structure and function, its links to disease, and its potential as a therapeutic target. It is distinct from a clinical trial testing a new anticancer effect.
The MYH9 gene encodes the heavy chain of non-muscle myosin IIA (NMIIA). Together with light chains, this heavy chain forms the NMIIA complex, which interacts with actin and uses energy from adenosine triphosphate (ATP) hydrolysis to generate mechanical force. It is part of the machinery cells need to move and divide.
Different roles in genetic disorders and cancer
MYH9 variants are known to cause MYH9-related disease (MYH9-RD), which is inherited in an autosomal dominant manner. Congenital thrombocytopenia and giant platelets are hallmark features; some patients also develop hearing loss or kidney abnormalities. MYH9's role in the development and progression of various cancers is also under study.
Whether MYH9 promotes or suppresses cancer depends on the cancer type and cellular context. The review summarizes evidence that MYH9 is involved in invasion, metastasis, and treatment resistance in several cancers, while noting that the same explanation cannot readily be applied to every cancer.
The review also discusses studies of MYH9 regulation by non-coding RNAs. In a study of a human ovarian adenocarcinoma cell line cited in the review, increased expression of the microRNA miR-6089 was reported to reduce cancer-cell proliferation, migration, and invasion, alongside directly targeting MYH9. These are cell-level observations and provide no basis for interpreting them as a treatment benefit in patients.
Questions remain about the relationship between genetic disorders and cancer. Current evidence does not establish whether people with MYH9 variants are more susceptible to cancer or, conversely, protected from it. MYH9 expression and function observed in tumors alone also cannot be used to predict cancer risk in people carrying inherited variants.
Therapeutic possibilities and limits to clinical translation
The researchers reviewed the possibility of targeting MYH9 or related regulatory pathways using non-coding RNAs, small-molecule drugs, and gene therapy. RNA interference (RNAi) is an approach to regulating gene expression, while small molecules are being studied as candidates that act on myosin activity or related signaling pathways. However, this review does not establish these approaches as proven MYH9-targeted cancer therapies.
CRISPR/Cas9 gene editing was also discussed as a potential future approach. The possibilities presented here should be distinguished from results demonstrating that correcting genetic variants produces anticancer effects or maximizes therapeutic efficacy. Tissue specificity, delivery efficiency, and off-target effects were identified as challenges to clinical translation. The myosin inhibitor blebbistatin also has limitations, including low water solubility, light-induced degradation, and toxicity.
This review brings together accumulated MYH9 research in genetics and oncology. Future work needs to clarify which functions should be modulated in specific cancers and assess the effects on normal cells. These questions must be addressed before discussing anticancer strategies tailored to an individual's genetic background.
Source: A review of MYH9 structure and function and its therapeutic implications in cancer and genetic disorders.
The myosin heavy chain 9 (MYH9) gene encodes non-muscle myosin heavy chain IIA (NMIIA), a vital protein involved in fundamental cellular activities, including movement, cell division, and signal transmission. Mutations in MYH9 were initially linked to autosomal dominant disorders collectively termed MYH9-related diseases (MYH9-RD). In recent years, MYH9 has gained significant attention for its pivotal roles in various cancers. However, despite extensive research, its exact contributions to cancer progression remain incompletely understood. Targeting MYH9 through approaches such as non-coding RNAs, small molecules, or gene therapy presents a promising avenue for advancing cancer treatment. Additionally, the dual role of MYH9 in MYH9-RD and cancer raises the intriguing question: are individuals with MYH9 mutations predisposed to or protected from cancer? This review aims to present the structure, functional significance, and clinical associations of MYH9, with an emphasis on its contributions to MYH9-RD and cancer progression. Furthermore, it examines MYH9's regulatory interactions with non-coding RNAs and its potential applications as a therapeutic target, offering insights into strategies such as RNA interference and CRISPR-based gene editing for cancer treatment.
MYH9 research could help identify candidate pathways for regulating cancer-cell migration and treatment resistance. For example, researchers could design studies in specific cancer models that target MYH9 or an RNA that regulates it and assess whether invasion or drug response changes. Such studies would need to examine not only cancer-cell responses but also effects on normal-cell function, delivery efficiency, and off-target effects. Because MYH9's role may vary by cancer type, the suitability of a uniform inhibition strategy also needs to be tested. Current evidence provides no basis for using MYH9 variants alone to predict an individual's cancer risk or establish personalized prevention guidance.