Abstract
Sexual dimorphism is observed in most human diseases. The difference in the physiology and genetics between sexes can contribute tremendously to the disease prevalence, severity, and outcome. Both hormonal and genetic differences between males and females can lead to differences in gene expression patterns that can influence disease risk and course. MicroRNAs have emerged as potential regulatory molecules in all organisms. They can have a broad effect on every aspect of physiology, including embryogenesis, metabolism, and growth and development. Numerous microRNAs have been identified and elucidated to play a key role in cardiovascular diseases, as well as in neurological and autoimmune disorders. This is especially important as microRNA-based tools can be exploited as beneficial therapies for disease treatment and prevention. Sex steroid hormones as well as X-linked genes can have a considerable influence on the regulation of microRNAs. However, there are very few studies highlighting the role of microRNAs in sex biased diseases. This review attempts to summarize differentially regulated microRNAs in males versus females in different diseases and calls for more attention in this underexplored area that should set the basis for more effective therapeutic strategies for sexually dimorphic diseases.
Highlights
Many complex regulatory steps are important in the conversion and dissemination of genetic information to molecular effectors
Sex differences can have major contributions in defining the course of these regulatory steps. Whether it is the presence of a Y chromosome, an extra X chromosome or a difference in the hormonal milieu, these gender differences are remarkably reflected in the disease outcomes
In recent years, microRNAs have emerged as powerful regulatory molecules
Summary
Many complex regulatory steps are important in the conversion and dissemination of genetic information to molecular effectors. MicroRNAs are involved in the regulation of virtually all cellular processes including metabolism, development, morphogenesis, programmed cell death, angiogenesis and so on [14,21,33,52,53,54,55,56,57] Their dysregulated expression is associated with human pathologies, including neurological disorders, cardiovascular diseases and cancer [27,28,30]. Administration of estrogens to castrated male NZB/WF1 mice resulted in the expression of female-associated systemic lupus erythematosus microRNAs including the miR-182 cluster, miR-379, and miR148a, demonstrating the role of sex hormones in the regulation of sexual dimorphism of microRNAs [84]. MiR-30b was shown to be regulated by estrogens and it is most likely under hormonal control [85] Another relevant study focused on the association of microRNAs on the X chromosome with high prevalence of schizophrenia in males compared to females. MiR-29 family members decrease the content of collagens by directly targeting them and block the process of development of fibrosis [88,138]
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