Influence of sex differences on microRNA gene regulation in disease

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.

miRNAs Differentially Expressed by Next-Generation Sequencing in Cord Blood Buffy Coat Samples of Boys and Girls

“…Previous miRNA studies [36,85], as well as our findings reported here, indicate the importance of accounting for sex differences when analyzing miRNA data. Similar observations have been reported for other epigenetic marks including DNA methylation and histone acetylation [28,[86][87].…”

Circulating microRNAs predict future fatal myocardial infarction in healthy individuals – The HUNT study

“…Gender differences in miR expression can often be explained by hormonal and genetic differences, as hormones and X-linked genes can influence the regulation of miRs [54]. However, there are just a few studies highlighting the role of miRs in sexually dimorphic disease [55,56].…”

Sex-Biased Gene Expression and Sexual Conflict throughout Development: Table 1.

“…At present, very little is known about miRNA functions, and even less is known about sexbiased expression patterns of miRNAs. These small RNAs could be extremely important, however, and are thought to have a role in the regulation of gene expression in sex-biased diseases (Sharma and Eghbali 2014), but far more data are needed before this can be discussed in detail.…”