MicroRNA-Regulated Pathways Associated with Endometriosis

Abstract

Endometriosis is a prevalent gynecological disease characterized by growth of endometriotic tissue outside the uterine cavity. MicroRNAs (miRNAs) are naturally occurring posttranscriptional regulatory molecules that potentially play a role in endometriotic lesion development. We assessed miRNA expression by microarray analysis in paired ectopic and eutopic endometrial tissues and identified 14 up-regulated (miR-145, miR-143, miR-99a, miR-99b, miR-126, miR-100, miR-125b, miR-150, miR-125a, miR-223, miR-194, miR-365, miR-29c and miR-1) and eight down-regulated (miR-200a, miR-141, miR-200b, miR-142-3p, miR-424, miR-34c, miR-20a and miR-196b) miRNAs. The differential expression of six miRNAs was confirmed by quantitative RT-PCR. An in silico analysis identified 3851 mRNA transcripts as putative targets of the 22 miRNAs. Of these predicted targets, 673 were also differentially expressed in ectopic vs. eutopic endometrial tissue, as determined by microarray. Functional analysis suggested that the 673 miRNA targets constitute molecular pathways previously associated with endometriosis, including c-Jun, CREB-binding protein, protein kinase B (Akt), and cyclin D1 (CCND1) signaling. These pathways appeared to be regulated both transcriptionally as well as by miRNAs at posttranscriptional level. These data are a rich and novel resource for endometriosis and miRNA research and suggest that the 22 miRNAs and their cognate mRNA target sequences constitute pathways that promote endometriosis. Accordingly, miRNAs are potential therapeutic targets for treating this disease.

Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis

“…Despite extensive research, the pathogenesis of endometriosis remains unclear because it is complex. Recently, several studies have revealed that aberrant miRNA profiles are correlated with endometriosis (Ohlsson Teague et al, 2009;Braza-Boïls et al, 2014;Rekker et al, 2015). In particular, our own and previous studies indicated that members of the miR-200 family (miR-200a, miR-200b, and miR-200c) were downregulated in endometriosis-associated tissues (Ohlsson Teague et al, 2009;Braza-Boïls et al, 2014;Rekker et al, 2015).…”

Overexpression of microRNA‐542‐3p attenuates the differentiating capacity of endometriotic stromal cells

“…There is accumulating data that miRNAs contribute to the pathogenesis of endometriosis by regulating abnormal cell differentiation, invasion, and inflammation 23. It has been reported that the expression of several miRNAs differs between the eutopic and ectopic endometrial tissues of women with and without endometriosis 9, 24. The authors recently reported that the down‐regulation of miR‐542‐3p expression in eutopic endometrial stromal cells enabled morphological and biological differentiation of the endometrium 13.…”

General Guidelines for Authors for Submission of Manuscripts that Contain Molecular Biological Content

“…Filtered gene lists provided as supplemental data must be provided as Excel spreadsheets and not PDFs. Specific examples of supplemental data accompanying gene expression profiling manuscripts can be found in Ohlsson Teague et al (2009); supplemental data available at: (http://mend.endojournals.org/cgi/content/full/ me.2008-0387/DC1).…”