Non-coding RNAs in endometriosis: a narrative review

BACKGROUND: Endometriosis is a benign gynaecological disorder, which affects 10% of reproductive-aged women and is characterized by endometrial cells from the lining of the uterus being found outside the uterine cavity. However, the pathophysiological mechanisms causing the development of this heterogeneous disease remain enigmatic, and a lack of effective biomarkers necessitates surgical intervention for diagnosis. There is international recognition that accurate non-invasive diagnostic tests and more effective therapies are urgently needed. Non-coding RNA (ncRNA) molecules, which are important regulators of cellular function, have been implicated in many chronic conditions. In endometriosis, transcriptome profiling of tissue samples and functional in vivo and in vitro studies demonstrate that ncRNAs are key contributors to the disease process. OBJECTIVE AND RATIONALE: In this review, we outline the biogenesis of various ncRNAs relevant to endometriosis and then summarize the evidence indicating their roles in regulatory pathways that govern disease establishment and progression. SEARCH METHODS: Articles from 2000 to 2016 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: ncRNA and reproduction; ncRNA and endometriosis; miRNA and endometriosis; lncRNA and endometriosis; siRNA and endometriosis; endometriosis; endometrial; cervical; ovary; uterus; reproductive tract. All articles were independently screened for eligibility by the authors. OUTCOMES: This review integrates extensive information from all relevant published studies focusing on microRNAs, long ncRNAs and short inhibitory RNAs in endometriosis. We outline the biological function and synthesis of microRNAs, long ncRNAs and short inhibitory RNAs and provide detailed findings from human research as well as functional studies carried out both in vitro and in vivo, including animal models. Although variability in findings between individual studies exists, collectively, the extant literature justifies the conclusion that dysregulated ncRNAs are a significant element of the endometriosis condition. WIDER IMPLICATIONS: There is a compelling case that microRNAs, long non-coding RNAs and short inhibitory RNAs have the potential to influence endometriosis development and persistence through modulating inflammation, proliferation, angiogenesis and tissue remodelling. Rapid advances in ncRNA biomarker discovery and therapeutics relevant to endometriosis are emerging. Unravelling the significance of ncRNAs in endometriosis will pave the way for new diagnostic tests and identify new therapeutic targets and treatment approaches that have the potential to improve clinical options for women with this disabling condition.