Altered Differential Expression of Genes and microRNAs Related to Adhesion and Apoptosis Pathways in Patients with Different Phenotypes of Endometriosis

Abstract

We aim to investigate the expression of genes (MAPK1 and CAPN2) and microRNAs (miR-30a-5p, miR-7-5p, miR-143-3p, and miR-93-5p) involved in adhesion and apoptosis pathways in superficial peritoneal endometriosis (SE), deep infiltrating endometriosis (DE), and ovarian endometrioma (OE), and to evaluate whether these lesions share the same pathophysiological mechanisms. We used samples of SE (n = 10), DE (n = 10), and OE (n = 10), and endometrial biopsies of these respective patients affected with endometriosis under treatment at a tertiary University Hospital. Endometrial biopsies collected in the tubal ligation procedure from women without endometriosis comprised the control group (n = 10). Quantitative real-time polymerase chain reaction was performed. The expression of MAPK1 (p < 0.0001), miR-93-5p (p = 0.0168), and miR-7-5p (p = 0.0006) was significantly lower in the SE group than in the DE and OE groups. The expression of miR-30a (p = 0.0018) and miR-93 (p = 0.0052) was significantly upregulated in the eutopic endometrium of women with endometriosis compared to the controls. MiR-143 (p = 0.0225) expression also showed a statistical difference between the eutopic endometrium of women with endometriosis and the control group. In summary, SE showed lower pro-survival gene expression and miRNAs involved in this pathway, indicating that this phenotype has a different pathophysiological mechanism compared to DE and OE.

Downregulation of DROSHA: Could It Affect miRNA Biogenesis in Endometriotic Menstrual Blood Mesenchymal Stem Cells?

“…Furthermore, we linked these miRNAs to disease ( Table 1 ). The miRNAs miR-128-3p, miR-27a-3p, miR-27b-3p, miR-181a-5p, miR-181b-5p, miR-452-3p, miR-216a-5p, miR-216b-5p, and miR-93-5p are targets for future functional studies as they are related in endometriosis to diagnostic biomarkers [ 42 ], autophagy [ 43 ], and the regulation of inflammation, vascularization, and angiogenesis of the endometrium during the menstrual cycle and decidualization [ 44 ]; fibrosis modulation [ 45 ]; enhancement of cell proliferation, migration, and invasion [ 46 ]; expression influenced by E2 and BPA [ 44 ]; regulation of human endometrial stromal cell decidualization [ 55 ]; expression regulated by the menstrual cycle [ 42 ]; stromal cell invasion and migration [ 48 ]; expression exclusively in ectopic stromal cells [ 48 ]; and sustained cell proliferation, cellular adhesion, and apoptosis [ 52 ].…”

Regulated Cell Death in Endometriosis

“…Illustratively, a recent examination focusing on miRNAs governing adhesion and apoptosis revealed a noteworthy elevation in the expression levels of miR-93-5p and miR-7-5p in the cohorts afflicted with deep infiltrating endometriosis and endometrioma, as opposed to those presenting with lesions of superficial peritoneal endometriosis. Perhaps these results could help identify differences between pathological phenotypes of endometriosis [62].…”

The Pathological Role of miRNAs in Endometriosis

“…Several studies have reported changes in the expression of specific miRNAs in endometriotic lesions. These miRNAs include miR-1, miR-29c, miR-34c, miR-100, miR-141, miR-145, miR-183, miR-196b, miR-200a, miR-200b, miR-200c, miR-202, miR-365, and miR-375 [142]. Some of these miRNAs are known to play roles in processes such as Epithelial-Mesenchymal Transition (EMT), angiogenesis, cell proliferation, cell adhesion, and invasion [142,143].…”

“…These miRNAs include miR-1, miR-29c, miR-34c, miR-100, miR-141, miR-145, miR-183, miR-196b, miR-200a, miR-200b, miR-200c, miR-202, miR-365, and miR-375 [142]. Some of these miRNAs are known to play roles in processes such as Epithelial-Mesenchymal Transition (EMT), angiogenesis, cell proliferation, cell adhesion, and invasion [142,143]. EMT and angiogenesis are crucial components of the pathophysiology of endometriotic lesion formation.…”