Sex disparity in cancer: roles of microRNAs and related functional players

Abstract

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.

Sex differences in cancer mechanisms

“…In addition to differences in the expression levels of protein-coding genes located on the sex chromosomes, lncRNAs [147] and microRNAs (miRNAs) can also escape X inactivation and differ in expression between the sexes. The X-chromosome contains an unusually high number of miRNAs, 118 compared to an average of 40-50 on the autosomes [148]. These miRNAs are regulators of a diverse array of processes, many of which are relevant to cancer [131,149,150].…”

Gender medicine and oncology: report and consensus of an ESMO workshop

“…Generally, adult women mount stronger innate and adaptive immune responses, resulting in a faster clearance of pathogens and greater vaccine efficacy, but also contributing to their increased susceptibility to inflammatory and autoimmune diseases [25]. Given that the sex differences in the number and function of immune cells remain consistent across different species from fruit flies to humans, this seems to be an evolutionarily conserved trait [25], which may be partly explained by the localization of various genes and micro-RNAs to the X-chromosome [26,27]. In addition, the TLR7 gene, a member of the Toll-like receptor (TLR) gene family, which is fundamental for recognition of pathogens and activation of innate immune effectors, evades silencing by physiological X-chromosome inactivation in immune cells in women [28].…”

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

“…Notably, no evidence has been shown thus far to establish the influence of AMPK on Mfn1 in the setting of cerebral IRI. Accordingly, the goal of our study is to explore the protective effect of resveratrol in cerebral reperfusion injury and mitochondrial function and verify whether resveratrol modulates mitochondrial protection and neuronal viability via the AMPK‐Mfn1 pathways …”

“…Accordingly, the goal of our study is to explore the protective effect of resveratrol in cerebral reperfusion injury and mitochondrial function and verify whether resveratrol modulates mitochondrial protection and neuronal viability via the AMPK-Mfn1 pathways. 31,32 2 | MATERIALS AND METHODS…”