Sex differences are widely observed under various circumstances ranging from physiological processes to therapeutic responses, and a myriad of sex-biased genes have been identified. In recent years, transcriptomic datasets of microRNAs (miRNAs), an important class of non-coding RNAs, become increasingly accessible. However, comprehensive analysis of sex difference in miRNA expression has not been performed. Here, we identified the differentially-expressed miRNAs between males and females by examining the transcriptomic datasets available in public databases and conducted a systemic analysis of their biological characteristics. Consequently, we identified 73 female-biased miRNAs (FmiRs) and 163 male-biased miRNAs (MmiRs) across four tissues including brain, colorectal mucosa, peripheral blood, and cord blood. Our results suggest that compared to FmiRs, MmiRs tend to be clustered in the human genome and exhibit higher evolutionary rate, higher expression tissue specificity, and lower disease spectrum width. In addition, functional enrichment analysis of miRNAs show that FmiR genes are significantly associated with metabolism process and cell cycle process, whereas MmiR genes tend to be enriched for functions like histone modification and circadian rhythm. In all, the identification and analysis of sex-biased miRNAs together could provide new insights into the biological differences between females and males and facilitate the exploration of sex-biased disease susceptibility and therapy.
男性与女性不仅在身体结构上，还在生理功能、治疗反应等方面都有所差异。为研究性别差异相关的分子机制，大量的性别差异表达基因已被鉴定出来。而microRNA作为近年来非编码RNA的一个研究热点，已有大量的转录组数据集将其囊括，但目前还没有研究对 microRNA性别差异表达情况进行全面分析。本研究基于公共数据库中符合条件的microRNA转录组数据集，从脑、结肠直肠粘膜、外周血和脐带血四种组织中鉴定出73个女性高表达的microRNA和163个男性高表达microRNA，并对其生物学特性进行了系统分析。结果表明，与女性高表达的microRNA相比，男性高表达microRNA在基因组上更倾向于成簇分布，具有更高的进化速率、表达组织特异性和更低的疾病谱宽度。此外，microRNA的功能富集分析结果显示女性高表达的microRNA显著富集代谢和细胞周期相关功能，而男性高表达microRNA倾向于富集组蛋白修饰和昼夜节律等功能。鉴定和分析具有性别差异的microRNA可以为理解男女间生物学差异提供新的视角，并将有助于性别差异治疗方案的研究。





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