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. 2021 Sep 29:2021:5298006.
doi: 10.1155/2021/5298006. eCollection 2021.

The Role of miRNAs 340-5p, 92a-3p, and 381-3p in Patients with Endometriosis: A Plasma and Mesenchymal Stem-Like Cell Study

Affiliations

The Role of miRNAs 340-5p, 92a-3p, and 381-3p in Patients with Endometriosis: A Plasma and Mesenchymal Stem-Like Cell Study

Afshin Bahramy et al. Biomed Res Int. .

Abstract

Background: Endometriosis is the most prevalent gynecological disease with elusive etiology. The mysterious entity and the lack of noninvasive diagnostic methods affect women's lives negatively. This study is aimed at finding the relationship between miR-340-5p, 92a-3p, and miR-381-3p and the pathogenesis of endometriosis in endometrial mesenchymal stem-like cells (eMSCs) of endometriosis and assessing their potential as a noninvasive biomarker in plasma.

Methods: Peripheral blood and eMSC specimens were collected from suspected women of endometriosis before laparoscopy. Total RNA was isolated from plasma and cultured eMSCs to synthesize complementary DNA. The expression of miR-340-5p, miR-92a-3p, and miR-381-3p was analyzed by RT-qPCR. To understand these miRNAs' role, we also did a bioinformatic analysis.

Results: There was a downregulation of miR-340-5p, miR-92a-3p, and miR-381-3p in plasma, and the upregulation of miR-340-5p and the downregulation of miR-92a-3p and miR-381-3p in eMSCs of women with endometriosis. There was a positive concordance between the expression of miR-92a-3p and miR-381-3p in plasma and eMSCs. Our study also showed three genes, Solute Carrier Family 6 Member 8 (SLC6A8), Zinc Finger Protein 264 (ZNF264), and mouse double minute 2 (MDM2), as common targets of these miRNAs.

Conclusions: This study has been one of the first attempts to examine the expression of miR-340-5p, miR-92a-3p, and miR-381-3p in both plasma and eMSCs and revealed their possible role in endometriosis based on in silico analysis. Biomarkers pave the way to develop a new therapeutic approach to the management or treatment of endometriosis patients. Our result as a first report shows that combined levels of miRNAs 340-5p and 381-3p may have the potential to be utilized as diagnostic biomarkers for endometriosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Target genes overlap between three miRNAs. Circos plot shows miRNA-mRNA interactions; 17 common genes are targeted by three miRNAs—miR-340-5p, miR-92a-3p, and miR-381-3p. Ribbons start from an mRNA (leftmost) and end in a miRNA (rightmost); the color of the ribbons indicates the originating mRNAs. Ribbon thickness indicates which mRNAs interact the most with all three miRNAs; the outermost ring displays miRNA color (leftmost) (a). A Venn diagram representing the number of miRNAs' target genes in common between miRNet, miRTargetLink, and Mienturnet (b).
Figure 2
Figure 2
Gene set enrichment analysis performed by EnrichR of target genes of miR-340-5p, miR-381-3p, and miR-92a-3p in endometriosis. Top 10 enriched pathways by WikiPathways 2019 Human and KEGG 2019 Human correlated with miRNAs' target genes. The x-axis represents the number of genes, and the y-axis represents enriched pathway (a). Gene set enrichment analysis by EnrichR showed the top 10 enriched correlated miRNA's target genes in the library of Tissue Protein Expression from Human ProteomicsDB (b). Gene set enrichment analysis by EnrichR showed the top 10 enriched correlated miRNA's target genes in the PheWeb 2019 (c).
Figure 3
Figure 3
miRNAs' expression in the plasma of endometriosis patients (EMS) and nonendometriosis patients (N-EMS) was assessed by RT-qPCR. The P value shows statistical significance of results between the case and control groups used for variables with nonnormal distribution: miR-340-5p (a) and normal distribution miR-92a-3p (b) and miR-381-3p (c); n = 60 (30 endometriosis patients; 30 nonendometriosis patients) (US: insignificant, P value: P value < 0.05, ∗∗P value < 0.01, and ∗∗∗P value < 0.0001).
Figure 4
Figure 4
The results of ROC curve analysis for the diagnostic value of miRNAs 340-5p and 381-3p (a) and their combination (b), the area under the curve (AUC) 0.707, 0.721, and 0.764, respectively.
Figure 5
Figure 5
miRNAs' expression in the eMSCs of endometriosis patients (EMS) and nonendometriosis patients (N-EMS) was assessed by RT-qPCR. The P value shows statistical significance of results between the case and control groups used for variable normal distribution; n = 6 (3 endometriosis patients; 3 nonendometriosis patients) (CS: close to significant, P value: P value < 0.05, ∗∗P value < 0.01, and ∗∗∗P value < 0.0001).
Figure 6
Figure 6
The endometriosis stages and the possible role of miR-340-5p, miR-92a-3p, and miR-381-3p in endometriosis, their target genes, and related pathways. MMP9: matrix metalloproteinase-9; CCND1: cyclin D1; DNMT1: DNA methyltransferase 1; PIK3CA: Phosphatidylinositol-4, 5-Bisphosphate 3-Kinase Catalytic Subunit Alpha; IGF-1R: insulin-like growth factor receptor; c-MET: MET protooncogene, receptor tyrosine kinase; eIF4E: eukaryotic translation initiation factor 4E; TGFB1: transforming growth factor beta 1; ITGA5: integrin subunit alpha 5; BMPR2: bone morphogenetic protein receptor type 2. The well-known process and pathways in endometriosis are apoptosis, proliferation, invasion, migration, senescence, and EMT process.

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