In analyzing a multitude of molecular and epigenetic studies in the field of oncology, the conclusion naturally suggests that, similar to the action in cancer, micro-RNAs participate in the pathogenesis of endometriosis and control its spread and recurrence, influence the development of hypofertility, exerting both stimulatory and suppressor effects on certain group of genes. However, today, there is no generally accepted classification of micro-RNA groups affecting the development of endometriosis, and a number of studies demonstrate directly opposite data.
A systematic analysis of the role of micro-RNA in the pathogenesis of endometriosis was conducted by Ohlsson Teague et al. in 2010 based on many studies [13]. The paper confirmed the important role of micro-RNA in both the development of endometriosis and subfertility in it, and the prospects for using micro-RNA as a biomarker of this disease and a therapeutic tool. Depending on the effect produced by endometriosis, microRNAs were distributed by the authors into several groups: 1. Inhibitors of cell proliferation (miR-20a, miR-34c, miR-125a, miR-125b, miR-126, miR-143, miR-145, miR-221, miR-222) 2. Inductors / inhibitors of hypoxic shock (miR-20a, miR-16) 3. Inhibitors of the activity of the anti-apoptotic protein BCL2 (miR-15b, miR-16) 4. Tissue repair inhibitors and TGFb-1 and TGFb-2 activity (miR-1, miR-21, miR-141, miR-194) 5. Inhibitors of translation of the inflammatory and transcription inhibitors COX-2 (miR-16, miR-20a, miR-199a) 6. Protein modeling and degradation inhibitors of the extracellular matrix (collagens COL1A1, COL1A2, COL3A1, COL15A1 and osteonectin secreting factor SPARC), metastasis and oncogenesis inhibitors - miR-29a. 7. Inhibitors of angiogenesis (miR-1, miR-15b, miR-16, miR-20a, miR-126, miR-223). In addition, the authors proposed to consider miR-29a as a serum biomarker of endometriosis. An increase in serum levels other than endometriosis is described in breast cancer, ovarian cancer, leukemia and lung cancer. The main effects are associated with the stimulation of proliferation and the processes of cellular invasion.
To date, the number of micro-RNAs has significantly increased, the role of which has been proven in the pathogenesis of endometriosis and its symptoms, but their systemic analysis has not been carried out. SiHyun Cho et al. in 2015, described a significant decrease in the level of expression of let-7b, which is responsible for regulating the proliferation, inflammatory and immune response, and miR-135a in the serum of patients with endometriosis to the proliferative phase [14]. However, none of the let-7 subunits is a specific biomarker of endometriosis. Its main function is to influence the differentiation of cells. At the same time, parallel studies in patients with endometrial cancer, conducted by Muralidharan Jayaraman et al., Did not show significant differences in the level of the let-7 and miR-135 subunits from the control group [15]. However, the change in the level of the let-7 and miR-135a subunits was found in many extragenital malignant processes, which, together with the high dependence of their expression on the cycle phase, does not allow considering these markers as potential highly specific biomarkers of endometriosis. In many studies, the serum levels of miR-16, miR-122, miR191, miR-195, miR-199a were studied, which were significantly elevated in patients with endometriosis amid a decrease in miR-9 *, miR-17-5p, miR-20a, miR-22, miR-141 *, miR-145 *, miR-542-3p. However, deviations in the content of many of them are found in other tumors of epithelial origin (colorectal cancer, etc.), which does not allow to consider them as pathognomonic highly specific markers of endometriosis. Research Pospekhova N.I. et al. (2013) allowed the identification of micro-RNAs that are aberrantly expressed in breast and serum cancer sites [16]. These data completely correspond to data published by Wang F et al. in 2010, demonstrated that there are strong correlations between serum / plasma miRNA profiles and cancer tissues, indicating that miRNAs can be released from tissues and enter the circulation [17].
A significant contribution to the understanding of epigenetic factors in the development of endometriosis was made by studies of Freizullin L.Z. et al. (2016), [18]. They carried out a comparative analysis of miR-9-5p, miR-20b-5p, miR-139-3p, miR-193a-3p, miR-200a-5p, miR-210-5p, miR-376c-5p and miR -378a-5p in eutopic and ectopic endometrium and near the affected tissue site in patients with severe infiltrative form of endometriosis. A significant (10-fold) increase in the expression of miR-376c-5p (in some databases is denoted miR-368) was found in the ectopic endometrium compared with eutopic. The increased level of expression of miR-376c-5p, except for cases of endometriosis, was found only in prostatic carcinoma [19], and miR-376c - in gastric cancer [20]. In this case, high oncogenic, proliferative and metastatic activity of miR-376c in gastric cancer was detected, and its level in urine in patients with gastric cancer was significantly increased. These data suggest that in patients with a high level of miR-376c-5p, endometriosis may have a more aggressive course and a significant zone of spread, and also increases the risk of malignancy. However, this assumption requires further research. In studies of the profile of microRNA expression in dwarf mice [19], it was found that increasing the expression of miR-376c-5p increases their lifespan. This confirms the involvement of miR-376c-5p in the suppression of the natural processes of aging and apoptosis of cells, and possibly the survival of altered cells under the influence of unfavorable factors. Conducted by A.N. Shirshova et al. (2015), studies of miR-135a and miR-376c-5p miRNA expression and serum levels in patients with ovarian cancer revealed no significant differences from healthy patients [21], which, along with the above data, allows us to consider miR -376c-5p as a potential serum biomarker of endometriosis.