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

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.

Specific plasma microRNA profiles could be potential non-invasive biomarkers for biochemical pregnancy loss following embryo transfer

“…MiR-7 plays a role in trophoblasts' invasion via the TGF-β-Smad pathway [ 58 ]. MiR-92a-3p plays a role in endometriosis [ 59 ] and is associated with endometrial receptivity [ 60 ] and trophoblast invasion [ 61 ].…”

Small Non-Coding RNAs as New Biomarkers to Evaluate the Quality of the Embryo in the IVF Process

“…The second predicted miRNA by the BioMAI predicting system was miR-92a-3p which is associated with a higher success of blastocyst implantation [ 20 , 54 ]. The level of miR-92a-3p was also studied in the cases of endometriosis and PCOS [ 55 , 56 ] where the level was downregulated. Endometriosis, as well as PCOS, is a well-known reason for infertility that reduces the implantation rate after embryo transfer [ 57 , 58 ].…”

The role of the tumor microenvironment in colorectal cancer and the potential therapeutic approaches

“…VEGF, vascular endothelial growth factor; HIF1, hypoxiainducible factor-1; TGFβ, transforming growth factor-beta; ECM, extracellular matrix; MMPs, matrix metalloproteinases; RBC, red blood cell (EMT)-pro-angiogenic factors, and it can also facilitate other tumorigenesis mechanisms such as genome instability. 34,54,55 Although fibroblasts, immune cells, and endothelial cells produce a large portion of pro-inflammatory signals as tumor microenvironment components, they have also been shown to play an important role in tumorigenesis promotion through the secretion of cytokines and proteases from CAFs. 34 It has been shown that fibroblasts adjacent to the CRC cells express IL-6, FAPα, and SPINK3 as an inflammation-induced factor in CRC.…”

“…One of the most important promoters of tumorigenesis in colon cancer is inflammation 53 . Inflammation starts as a response of the immune system to pathogens or tissue damage; however, perpetuating this response results in increasing the incidence of cancer due to the weakness of the anti‐tumor response because it can release bioactive molecules from tumor microenvironment cells such as chemokines, cytokines, and growth factors—that contribute to constant proliferation and cell survival signals to prevent apoptosis‐metalloproteinases,—as a modifier of extracellular matrix to initiate epithelial‐mesenchymal transition (EMT)—pro‐angiogenic factors, and it can also facilitate other tumorigenesis mechanisms such as genome instability 34,54,55 . Although fibroblasts, immune cells, and endothelial cells produce a large portion of pro‐inflammatory signals as tumor microenvironment components, they have also been shown to play an important role in tumorigenesis promotion through the secretion of cytokines and proteases from CAFs 34 …”