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.
Shannon M. Hawkins et al. (2018) [22] revealed 10 activating (miR-202, miR-193a-3p, miR-29c, miR-708, miR-509-3-5p, miR-574-3p, miR-193a-5p, miR-485-3p, miR-100, and miR-720) and 12 inhibitors of the development of endometrioma microRNAs (miR-504, miR-141, miR-429, miR-203, miR-10a, miR-200b, miR-873, miR-200c, miR-200a, miR-449b, miR-375, and miR-34c-5p) among 286 individual microRNAs studied in patients with endometriosis.
The greatest deviations in serum in patients with endometriosis were found in the levels of two microRNAs: a significant, almost 4-fold increase in the content of miR-29c and a 2.5-fold decrease in miR-200b. At the same time, the authors found no changes in the level of miR-191, which is proposed by Mei Dong et al. [23] as a potential biomarker of endometriosis. In addition, an increase in the level of miR-191 is proven in ovarian cancer and colorectal cancer, which casts doubt on the possibility of using it as a biomarker of endometriosis.
A significant advantage of micro-RNA as a potential serum biomarker of endometriosis, in contrast to, for example, genetic screening, is the high stability of micro-RNA molecules in both serum and other biological fluids and in vitro, along with their intactness, as well as a lower the cost of methods for their detection.
Thus, the serum micro-RNA looks very promising in the search for a highly specific and reliable endometriosis biomarker.
However, in order to clarify the specificity of the biomarker, further research is needed, including analysis of other diseases of the female reproductive system.