The Role of MicroRNA, Long Non-Coding RNA and Circular RNA in the Pathogenesis of Polycystic Ovary Syndrome: A Literature Review

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disease in females of reproductive age, affecting 4–20% of pre-menopausal women worldwide. MicroRNAs (miRNAs) are endogenous, single-stranded, non-coding, regulatory ribonucleic acid molecules found in eukaryotic cells. Abnormal miRNA expression has been associated with several diseases and could possibly explain their underlying pathophysiology. MiRNAs have been extensively studied for their potential diagnostic, prognostic, and therapeutic uses in many diseases, such as type 2 diabetes, obesity, cardiovascular disease, PCOS, and endometriosis. In women with PCOS, miRNAs were found to be abnormally expressed in theca cells, follicular fluid, granulosa cells, peripheral blood leukocytes, serum, and adipose tissue when compared to those without PCOS, making miRNAs a useful potential biomarker for the disease. Key pathways involved in PCOS, such as folliculogenesis, steroidogenesis, and cellular adhesion, are regulated by miRNA. This also highlights their importance as potential prognostic markers. In addition, recent evidence suggests a role for miRNAs in regulating the circadian rhythm (CR). CR is crucial for regulating reproduction through the various functions of the hypothalamic-pituitary-gonadal (HPG) axis and the ovaries. A disordered CR affects reproductive outcomes by inducing insulin resistance, oxidative stress, and systemic inflammation. Moreover, miRNAs were demonstrated to interact with lncRNA and circRNAs, which are thought to play a role in the pathogenesis of PCOS. This review discusses what is currently understood about miRNAs in PCOS, the cellular pathways involved, and their potential role as biomarkers and therapeutic targets.