Differential Expression of MicroRNAs between Eutopic and Ectopic Endometrium in Ovarian Endometriosis

Abstract

Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a common gynecological disease with poorly understood pathogenesis. MicroRNAs are members of a class of small noncoding RNA molecules that have a critical role in posttranscriptional regulation of gene expression by repression of target mRNAs translation. We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium in 3 patients through microarray analysis. We identified 50 microRNAs differentially expressed and the differential expression of five microRNAs was validated by real-time RT-PCR in other 13 patients. We identified in silico their predicted targets, several of which match the genes that have been identified to be differentially expressed in ectopic versus eutopic endometrium in studies of gene expression. A functional analysis of the predicted targets indicates that several of these are involved in molecular pathways implicated in endometriosis, thus strengthening the hypothesis of the role of microRNAs in this pathology.

Expression of miR-126 and Crk in endometriosis: miR-126 may affect the progression of endometriosis by regulating Crk expression

“…Less evidence has demonstrated the roles of miR-126 and Crk in the pathogenesis of EMs. Our present study confirmed that ECs expresses less miR-126 than EUs, further validating the results of previous miRNA profiling studies of EMs [25,[32][33][34]. The present study may provide initial evidence that miR-126 may participate [35,36].…”

MiR-199a attenuates endometrial stromal cell invasiveness through suppression of the IKK /NF- B pathway and reduced interleukin-8 expression

“…In agreement with our results, Pan et al (2007) have identified that miR-199a is down-regulated in endometriotic tissues in comparison with normal endometrium. However, down-regulation of miR-199a was not reported by other studies on miRNA expression in endometriosis (Burney et al, 2009;Ohlsson Teague et al, 2009;Filigheddu et al, 2010;Hawkins et al, 2011;Ramon et al, 2011). This is likely due to the difference between the study designs, methods of analysis, menstrual cycle phase at the time of biopsy and patient cohorts used in their study when compared with ours.…”

“…6). MiRNAs are small, non-coding RNAs that are frequently dysregulated in female reproductive pathologies, including endometriosis (Pan et al, 2007;Toloubeydokhti et al, 2008;Burney et al, 2009;Carletti and Christenson, 2009;Ohlsson Teague et al, 2009;Filigheddu et al, 2010;Hawkins et al, 2011;Ramon et al, 2011). In the present report, we observed that the expression level of miR-199a was lower in the eutopic endometrium from women with endometriosis, and even lower in the paired ovarian endometrioma, compared with the expression in normal controls.…”

“…Furthermore, miR-199a can target IkappaB kinase beta (IKKb) (Chen et al, 2008), a co-factor required for nuclear factor-kappa B (NF-kB) pathway activation, which may drive the expression of several genes related to malignant transformation. Recently, multiple published studies have identified differentially expressed miRNAs in endometriotic tissues (Pan et al, 2007;Toloubeydokhti et al, 2008;Burney et al, 2009;Ohlsson Teague et al, 2009;Filigheddu et al, 2010;Hawkins et al, 2011; † Lan Dai and Liying Gu contributed equally to this work. Ramon et al, 2011), and the results of one research study suggest that miR-199a may decrease in endometriosis (Pan et al, 2007).…”

The diversity of sex steroid action: the role of micro-RNAs and FOXO transcription factors in cycling endometrium and cancer

“…Endometriosis affects as many as 10% of all women of reproductive age and is a major cause of pelvic pain and conception delay. Microarray analyses have been employed to identify differentially expressed miRNAs in paired eutopic endometrium and ectopic lesions (Filigheddu et al 2010, Teague et al 2010. Although one study yielded 22 differentially expressed miRNAs and another 50 species, the validity of this approach is somewhat questionable, as endometriotic implants differ profoundly in architecture and cellular composition when compared with eutopic endometrium.…”