The diagnostic role of microRNAs as biological markers of external (retrocervical) endometriosis
Objective. To analyze the data available in the current literature on the role of microRNAs as biological markers of external genital endometriosis.Almova I.K., Bobrov M.Yu., Chuprynin V.D., Khilkevich E.G., Chursin V.V., Melnikov M.V., Buralkina N.A., Veredchenko A.V.
Material and methods. The review includes the data of foreign and Russian authors, which have been found in PubMed, by using the key words: biomarkers of endometriosis; microRNAs and endometriosis; and biomarkers of external genital endometriosis. The search depth was 5 years.
Results. The differential expression of microRNAs in the eutopic and ectopic endometrium may suggest that microRNAs can play an important role in the development of endometrioid lesions. It is proven that miRNAs are active regulators of gene expression in endometriosis and associated reproductive dysfunctions. Detection of circulating miRNAs in plasma and other biological fluids in terms of their relative stability increases the likelihood that they may be investigated and proposed as non-invasive biomarkers for the diagnosis of endometriosis. Development of new exposure methods that can block the expression or mimic the function of miRNAs can represent new facets of treatment and prevention of a disease recurrence.
Conclusion. The investigations confirm the prospects and relevance of studying the role of microRNAs as diagnostic markers of external genital endometriosis. The development of non-invasive biomarkers will be able to substantially reduce the time of diagnosis of external genital endometriosis, followed by timely treatment.
Keywords
biomarkers
microRNA
endometriosis
eutopic and ectopic endometrium
gene expression
infertility
pelvic pain
Supplementary Materials
- Table 1. Comparison of microRNA expression characteristics in foci of endometriosis and control groups [0 1]
- Table 2. microRNAs differentially expressed in the lesions compared with EGE eutopic endometrium [0 1]
References
1. Sourial S., Tempest N., Hapangama D.K. Theories on the pathogenesis of endometriosis. Int. J. Reprod. Med. 2014; 2014: 179515. doi: 10.1155/2014/179515.
2. Адамян Л.В., Андреева Е.Н., Аполихина И.А., Беженарь В.Ф., Геворкян М.А., Гус А.И., Демидов В.Н., Калинина Е.А., Леваков С.А., Марченко Л.А., Попов А.А., Сонова М.М., Хашукоева А.З., Чернуха Г.Е., Яроцкая Е.Л. Эндометриоз: диагностика, лечение, реабилитация. Федеральные клинические рекомендации по ведению больных. М.: Российское общество акушеров-гинекологов; 2013. [Adamyan L.V., Andreeva E.N., Apolikhina I.A., Bezhenar V.F., Gevorkyan M.A., Gus A.I., Demidov V.N., Kalinina E.A., Levakov S.A., Marchenko L.A., Popov A.A., Sonova M.M., Khashukoeva A.Z., Chernukha G.E., Yarotskaya E.L. Endometriosis: Diagnosis, treatment and rehabilitation. Federal guidelines for the management of patients. Moscow: Russian Society of Obstetricians and Gynecologists; 2013. (in Russian)]
3. Zhang J., Huang F. Epigenetics: an emerging research field of infertility associated with endometriosis. Int. J. Clin. Exp. Med. 2016; 9(10): 18883-9.
4. Clarke-Pearson D.L., Geller E.J. Complications of hysterectomy. Obstet. Gynecol. 2013; 121(3): 654-73.
5. Dunselman G.A., Vermeulen N., Becker C., Calhaz-Jorge C., D’Hooghe T., De Bie B. et al. ESHRE guideline: management of women with endometriosis. Hum. Reprod. 2014; 29: 400-12.
6. Gilabert-Estelles J., Braza-Boils A., Ramon L.A., Zorio E., Medina P., España F., Estellés A. Role of microRNAs in gynecological pathology. Curr. Med. Chem. 2012; 19(15): 2406-13. doi: 10.2174/092986712800269362.
7. Ibrahim S.A., Hassan H., Götte M. MicroRNA-dependent targeting of the extracellular matrix as a mechanism of regulating cell behavior. Biochim. Biophys. Acta. 2014; 1840(8): 2609-20. doi: 10.1016/j.bbagen.2014.01.022.
8. Hull M.L., Nisenblat V. Tissue and circulating microRNA influence reproductive function in endometrial disease. Reprod. Biomed. Online. 2013; 27(5): 515-29. doi: 10.1016/j.rbmo.2013.07.012.
9. Yang L., Liu H.Y. Small RNA molecules in endometriosis: pathogenesis and therapeutic aspects. Eur. J. Obstet. Gynecol. Reprod. Biol. 2014; 183: 83-8. doi: 10.1016/j.ejogrb.2014.10.043.
10. Saare M., Rekker K., Laisk-Podar T., Rahmioglu N., Zondervan K., Salumets A. et al. Challenges in endometriosis miRNA studies - From tissue heterogeneity to disease specific miRNAs. Biochim. Biophys. Acta. 2017; 1863(9): 2282-92. doi: 10.1016/j.bbadis.2017.06.018.
11. Ramón L.A., Braza-Boïls A., Gilabert-Estellés J., Gilabert J., España F., Chirivella M., EstellésA. microRNAs expression in endometriosis and their relation to angiogenic factors. Hum. Reprod. 2011; 26(5): ()1082-1090. doi: 10.1093/humrep/der025.
12. Dong M., Yang P., HuaF. MiR-191 modulates malignant transformation of endometriosis through regulating TIMP3. Med. Sci. Monit. 2015; 21: 915-920. doi: 10.12659/MSM.893872
13. Graham A., Falcone T., Nothnick W.B. The expression of microRNA-451 in human endometriotic lesions is inversely related to that of macrophage migration inhibitory factor (MIF) and regulates MIF expression and modulation of epithelial cell survival. Hum. Reprod. 2015; 30(3): 642-652. doi: 10.1093/humrep/dev005
14. Shen L., Yang S., Huang W., Xu W., Wang Q., Song Y., Liu Y. MicroRNA23a and MicroRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis. J. Clin. Endocrinol. Metab. 2013; 98(4): 1575-82. doi: 10.1210/jc.2012-3010.
15. Long M., Wan X., La X., Gong X., Cai X. miR-29c is downregulated in the ectopic endometrium and exerts its effects on endometrial cell proliferation, apoptosis and invasion by targeting c-Jun. Int. J. Mol. Med. 2015; 35(4): 1119-25. doi: 10.3892/ijmm.2015.2082.
16. Zheng B., Xue X., Zhao Y., Chen J., Xu C.Y., Duan P. The differential expression of microRNA-143,145 in endometriosis. Iran. J. Reprod. Med. 2014; 12(8):555-60.
17. Saare M., Rekker K., LaiskPodar T., Sõritsa D., Roost A., Simm J. et al. High-throughput sequencing approach uncovers the miRNome of peritoneal endometriotic lesions and adjacent healthy tissues. PLoS One. 2014; 9(11): e112630. doi: 10.1371/journal.pone.0112630.
18. Marí-Alexandre J., Sánchez-Izquierdo D., Gilabert-Estellés J., Barceló-Molina M., Braza-Boïls A., Sandoval J. miRNAs regulation and its role as biomarkers in endometriosis. Int. J. Mol. Sci. 2016; 17(1): pii: E93. doi: 10.3390/ijms17010093.
19. Shi X.Y., Gu L., Chen J., Guo X.R., Shi Y.L. Downregulation of miR-183 inhibits apoptosis and enhances the invasive potential of endometrial stromal cells in endometriosis. Int. J. Mol. Med. 2014; 33: 59-67. doi: 10.3892/ijmm.2013.1536.
20. Yang R., Teng H., Xu X., Liu S., Wang Y., Guo F., Liu X. Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis. Genet. Mol. Res. 2016; 15(2). doi: 10.4238/gmr.15027826.
21. Braza-Boïls A., Marí-Alexandre J., Gilabert J., Sánchez-Izquierdo D., España F., Estellés A., Gilabert-Estellés J. MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors. Hum. Reprod. 2014; 29(5): 978-88. doi: 10.1093/humrep/deu019.
22. Yang Y.M., Yang W.X. Epithelial-to-mesenchymal transition in the development of endometriosis. Oncotarget. 2017; 8(25): 41679-89. doi: 10.18632/oncotarget.16472.
23. Park S.M., Gaur A.B., Lengyel E., Peter M.E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008; 22(7): 894-907. doi: 10.1101/gad.1640608.
24. Gregory P.A., Bracken C.P., Smith E., Bert A.G., Wright J.A., Roslan S. et al. An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol. Biol. Cell. 2011; 22(10): 1686-98. doi: 10.1091/mbc.E11-02-0103.
25. Avgeris M., Stravodimos K., Fragoulis E.G., Scorilas A. The loss of the tumour-suppressor miR-145 results in the shorter disease-free survival of prostate cancer patients. Br. J. Cancer. 2013; 108(12): 2573-81. doi: 10.1038/bjc.2013.250.
26. Rekker K., Saare M., Roost A.M., Salumets A., Peters M. Circulating microRNA profile throughout the menstrual cycle. PLoS One. 2013; 8(11): e81166. doi: 10.1371/journal.pone.0081166. eCollection 2013.
27. Ohlsson Teague E.M.C., Van der Hoek K.H., Van der Hoek M.B., Perry N., Wagaarachchi P., Robertson S.A., Print C.G., HullL.M. MicroRNA-regulated pathways associated with endometriosis. Mol. Endocrinol. 2009; 23(2): 265-275. doi: 10.1210/me.2008-0387.
28. Filigheddu N., Gregnanin I., Porporato P.E., Surico D., Perego B., Galli L., Patrignani C., Graziani A., Surico N. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J. Biomed. Biotechnol. 2010; 2010: 369549. doi: 10.1155/2010/369549.
29. Hawkins S.M., Creighton C.J., Han D.Y., Zariff A., Anderson M.L., Gunaratne P.H., Matzuk M.M. Functional microRNA involved in endometriosis. Mol. Endocrinol. 2011; 25(5): 821-32. doi: 10.1210/me.2010-0371.
30. Kent O.A., McCall M.N., Cornish T.C., Halushka M.K. Lessons from miR-143/145: the importance of cell-type localization of miRNAs. Nucleic Acids Res. 2914; 42(12): 7528-38. doi: 10.1093/nar/gku461.
31. Dai L., Gu L., Di W. MiR-199a attenuates endometrial stromal cell invasiveness through suppression of the IKKβ/NF-κB pathway and reduced interleukin-8 expression. Mol. Hum. Reprod. 2012; 18: 136-45. doi: 10.1093/molehr/gar066.
32. Adammek M., Greve B., Kässens N., Schneider C., Brüggemann K., Schüring A.N. et al. MicroRNA miR-145 inhibits proliferation, invasiveness, and stem cell phenotype of an in vitro endometriosis model by targeting multiple cytoskeletal elements and pluripotency factors. Fertil. Steril. 2013; 99(5): 1346-55. e5. doi: 10.1016/j.fertnstert.2012.11.055.
33. Kachgal S., Mace K.A., Boudreau N.J. The dual roles of homeobox genes in vascularization and wound healing. Cell Adh. Migr. 2012; 6(6): 457-70. doi: 10.4161/cam.22164.
34. Liu S., Gao S., Wang X.Y., Wang D.B. Expression of miR-126 and Crk in endometriosis: miR-126 may affect the progression of endometriosis by regulating Crk expression. Arch. Gynecol. Obstet. 2012; 285(4): 1065-72. doi: 10.1007/s00404-011-2112-6.
35. Zhang D., Li Y., Tian J., Zhang H., Wang S. MiR-202 promotes endometriosis by regulating SOX6 expression. Int. J. Clin. Exp. Med. 2015; 8(10):17757-64.
36. Rogers P.A., D’Hooghe T.M., Fazleabas A., Giudice L.C., Montgomery G.W., Petraglia F., Taylor R.N. Defining future directions for endometriosis research: workshop report from the 2011 World Congress of Endometriosis in Montpellier, France. Reprod. Sci. 2013; 20(5): 483-99. doi: 10.1177/1933719113477495.
37. Estella C., Herrer I., MorenoMoya J.M., Quiñonero A., Martínez S., Pellicer A., Simónmi C. RNA signature and Dicer requirement during human endometrial stromal decidualization in vitro. PLoS One. 2012; 7(7): e41080. doi: 10.1371/journal.pone.0041080.
38. Altmäe S., Martinez-Conejero J.A., Esteban F.J., Ruiz-Alonso M., Stavreus-Evers A., Horcajadas J.A., Salumets A. MicroRNAs miR-30b, miR-30d, and miR-494 regulate human endometrial receptivity. Reprod. Sci. 2013; 20(3): 308-17. doi: 10.1177/1933719112453507.
39. Fassbender A., Burney R.O., Dorien F. O., D’Hooghe T., Giudice L. Update on biomarkers for the detection of endometriosis. Biomed. Res. Int. 2015; 2015: 130854. doi: 10.1155/2015/130854.
40. Laudanski P., Charkiewicz R., Kuzmicki M., Szamatowicz J., Charkiewicz A., Niklinski J. MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis. Reprod. Biol. Endocrinol. 2013; 11: 78. doi: 10.1186/1477-7827-11-78.
41. Wang W.T., Zhao Y.N., Han B.W., Hong S.J., Chen Y.Q. Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis. J. Clin. Endocrinol. Metab. 2013; 98(1): 281-9. doi: 10.1210/jc.2012-2415.
42. Jia S.Z., Yang Y., Lang J., Sun P., Leng J. Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis. Hum. Reprod. 2013; 28(2): 322-30.
43. Meijer H.A., Smith E.M., Bushell M. Regulation of miRNA strand selection: follow the leader? Biochem. Soc. Trans. 2014; 42(4): 1135-40. doi: 10.1042/BST20140142.
Received 13.03.2017
Accepted 28.04.2017
About the Authors
Almova Indira K., postgraduate student of the Surgical Department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79054357317. E-mail: www.gold11@mail.ru
Bobrov Mikhail Yu., Ph.D., Head of the Laboratory of Molecular Pathophysiology, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79032518677. E-mail: mbobr@mail.ru
Chuprynin Vladimir Dmitrievich, PhD, Head of the Department of General Surgery, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954383575. E-mail: v_chuprynin@oparina4.ru
Khilkevich Elena Grigorevna, leading researcher of General Surgery, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387783. E-mail: e_khilkevich@oparina4.ru
Chursin Vyacheslav Vladimorovich, doctor surgeon of General Surgery, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387833. E-mail:v_chursen@oparina4.ru
Melnikov Mikhail Viktorovich, Candidate of Medical Sciences, Head in Clinical Work, Department of Surgery, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387833
Buralkina Natalya Aleksandrovna, doctor of Medical Sciences, Senior Researcher, the second gynecological department, Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387833. E-mail: n_buralkina@oparina4.ru
Veredchenko Aleksandr Viktorovich, candidate of medical sciences, doctor surgeon of General Surgery, Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387833. E-mail: a_veredchenko@oparina4.ru
For citations: Almova I.K., Bobrov M.Yu., Chuprynin V.D., Khilkevich E.G., Chursin V.V., Melnikov M.V., Buralkina N.A., Veredchenko A.V. The diagnostic role of microRNAs as biological markers of external (retrocervical) endometriosis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (8): 34-40. (in Russian)
http://dx.doi.org/10.18565/aig.2017.8.34-40
Similar Articles
