Oncology Unit, Center for Gender-specific Medicine Istituto Superiore di Sanita', Viale Regina Elena, 299 00161, Rome, Italy.
Immunotherapy Unit, Department of Oncology and Molecular Medicine, Istituto Superiore di Sanita', Viale Regina Elena, 299 00161, Rome, Italy.
Cell Death Differ. 2018 Mar;25(3):477-485. doi: 10.1038/s41418-017-0051-x. Epub 2018 Jan 19.
A sexual dimorphism at the cellular level has been suggested to play a role in cancer onset and progression. In particular, very recent studies have unraveled striking differences between cells carrying XX or XY chromosomes in terms of response to stressful stimuli, indicating the presence of genetic and epigenetic differences determining sex-specific metabolic or phenotypic traits. Although this field of investigation is still in its infancy, available data suggest a key role of sexual chromosomes in determining cell life or death. In particular, cells carrying XX chromosomes exhibit a higher adaptive potential and survival behavior in response to microenvironmental variations with respect to XY cells. Cells from females also appear to be equipped with more efficient epigenetic machinery than the male counterpart. In particular, the X chromosome contains an unexpected high number of microRNAs (miRs), at present 118, in comparison with only two miRs localized on chromosome Y, and an average of 40-50 on the autosomes. The regulatory power of these small non-coding RNAs is well recognized, as 30-50% of all protein-coding genes are targeted by miRs and their role in cell fate has been well demonstrated. In addition, several further insights, including DNA methylation patterns that are different in males and females, claim for a significant gender disparity in cancer and in the immune system activity against tumors. In this brief paper, we analyze the state of the art of our knowledge on the implication of miRs encoded on sex chromosomes, and their related functional paths, in the regulation of cell homeostasis and depict possible perspectives for the epigenetic research in the field.
细胞水平上的性别二态性被认为在癌症的发生和发展中起作用。特别是，最近的研究揭示了携带 XX 或 XY 染色体的细胞在应激刺激反应方面存在显著差异，表明存在决定性别特异性代谢或表型特征的遗传和表观遗传差异。尽管这一研究领域仍处于起步阶段，但现有数据表明性染色体在决定细胞生死方面起着关键作用。特别是，携带 XX 染色体的细胞在应对微环境变化时表现出更高的适应性潜力和生存行为，而 XY 细胞则不然。女性细胞似乎还配备了比男性细胞更有效的表观遗传机制。特别是，X 染色体包含了数量惊人的 miRNA（miRs），目前有 118 个，而 Y 染色体上只有两个，常染色体上平均有 40-50 个。这些小非编码 RNA 的调控作用是众所周知的，因为 30-50%的蛋白质编码基因都受到 miRs 的靶向调控，它们在细胞命运中的作用也得到了很好的证明。此外，包括男性和女性之间不同的 DNA 甲基化模式在内的其他一些新发现，表明在癌症和免疫系统对肿瘤的反应中存在显著的性别差异。在这篇简短的论文中，我们分析了我们对性染色体上编码的 miRNAs 及其相关功能途径在细胞内稳态调控中的作用的最新认识，并描绘了该领域中表观遗传研究的可能前景。
