A Review of microRNAs in the Post-transcriptional Regulation and its Clinical Manifestation in the Polycystic Ovary Syndrome.

MicroRNAs (miRNAs) are single stranded, short, non-coding, and highly conserved RNA molecules with around 22 nucleotides. They regulate gene expression at the co- and post-transcriptional levels. The accumulated research reports showed dysregulated miRNA expression in various female reproductive disorders most notably polycystic ovary syndrome (PCOS). PCOS is an endocrine disorder that affects women of reproductive age. The clinical manifestations of this disease are dominated by hyperandrogenism, polycystic ovaries, and chronic anovulation. Recently, evidence has confirmed abnormal expression of miRNAs in theca cells, granulosa cells, follicular fluid, blood, and serum of women with PCOS. Although some of these reports are controversial, the variability could be attributed to different analysis methods and small sample sizes. Overall, these findings point toward the role of miRNAs in the occurrence and progression of PCOS. However, the exact mechanism of its etiology largely remains unknown. This review takes us beyond the traditional localized dysregulation to explore the regulatory role of the gut microbiota-miRNA axis, exosomal miRNAs and the complexity of competitive endogenous RNA (ceRNA) networks where long non coding RNAs (lncRNAs) and circular RNAs (circRNAs) act as sponges to modulate miRNA activity. miRNAs can be used as pharmacogenomic biomarkers to predict the therapeutic responses to clinical interventions through the integration of machine learning algorithms for enhanced diagnostic accuracy. While research investigations are predominantly based on in vitro and clinical samples, we emphasize the need for more in vivo research to decode the precise etiology of PCOS. This review provides comprehensive update on the functional and clinical potential of miRNAs as non-invasive biomarkers and therapeutic targets for the management of PCOS.