Long non-coding RNAs: novel players in the pathogenesis of polycystic ovary syndrome - PubMed (original) (raw)

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Long non-coding RNAs: novel players in the pathogenesis of polycystic ovary syndrome

Mixue Tu et al. Ann Transl Med. 2021 Jan.

Abstract

Long non-coding RNAs (lncRNAs) are a class of transcripts (>200 nucleotides) lacking protein-coding capacity. Based on the complex three-dimensional structure, lncRNAs are involved in many biological processes and can regulate the expression of target genes at chromatin modification, transcriptional and post-transcriptional levels. LncRNAs have been studied in multiple diseases but little is known about their role(s) in polycystic ovary syndrome (PCOS), the most common endocrinological disorder in reproductive-aged women around the world. In this review, we characterized and explored the potential mechanisms of lncRNAs in the pathogenesis of PCOS. We found that lncRNAs play a molecular role in PCOS mainly by functioning as the competitive endogenous RNA (ceRNA) and are significantly correlated with some clinical phenotypes. We summarized in detail regarding aberrant lncRNAs in different specimens of women with PCOS [i.e., granulosa cells (GCs), cumulus cells (CCs), follicular fluid (FF), peripheral blood] and various PCOS rodent models [i.e., dehydroepiandrosterone (DHEA) and letrozole induced models]. In clinical practice, detection of lncRNAs in serum might enable early diagnosis. Furthermore, new lncRNA-based classifications might be emerging as potent predictors of a particular phenotype in PCOS. Overall, we proposed new insights for the application of precision medicine approaches to the management of PCOS.

Keywords: Long non-coding RNAs; cumulus cells (CCs); granulosa cells (GCs); oocyte; polycystic ovary syndrome (PCOS).

2021 Annals of Translational Medicine. All rights reserved.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at: http://dx.doi.org/10.21037/atm-20-5044). Dr. DZ, Dr. LM, Dr. YW, and MT report grants from National Key Research & Developmental Program of China, grants from National Natural Science Foundation of China, during the conduct of the study.

Figures

Figure 1

Figure 1

Identified lncRNA in PCOS. (A) LncRNA profile are depicted in ovarian issue from PCOS patients and rodent model. The function of most listed lncRNAs has not been investigated; (B) LncRNA signatures in follicles are key for uncovering the pathophysiologic mechanism in PCOS. The studies in granulosa cells are the most, and those lncRNA work maily through ceRNA network and some other identified singaling pathways (i.e., p53 pathway, NF-κB pathway). Little is know about the lncRNA function in follicular fluid. Therefore, we hypothesis that lncRNAs are transported from GCs to oocyte via extracellular vesicles, regulating the gene expression in oocyte during the follicle development. Several lncRNA are reported to be involved in the development of human follicle and regulate the transcription and RNA processing in paraspeckle, but the blanks about the lncRNAs signature in oocyte of PCOS urgently need to be filled in to better understand the molecular mechanism of ovarian follicular arrest; (C) LncRNA detected in peripherial blood are associated with endocrine changes (i.e., lipid metabolism, androgen metabolism, glucose or insulin metabolism) and even connected with the pregnant outcome, providing new insights for our further understand of lncRNAs in PCOS and expand the novel diagnostic biomarkers and therapeutic targets.

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