Assessment of microRNA expression in retrocervical endometriotic lesions
Aim. To profile microRNA in the tissues of the ectopic and eutopic endometrium and identify signaling pathways and processes regulated by differentially expressed microRNAs. Material and methods. Differentially expressed microRNAs were detected using the next-generation sequencing technique. The sequencing data were validated by real-time polymerase chain reaction. Signaling pathways and processes were estimated by enriching information databases with bioinformatic analysis. Results. RNA sequencing resulted in the identification of 429 miRNAs with different patterns in the tissues of the eutopic and ectopic endometrium. As a result of statistical analysis based on the reliability of differences and representation in all comparison groups, 85 miRNAs were selected to determine the possible involvement of their target genes in intracellular cascades and the processes regulated by them. Bioinformatic analysis showed the involvement of regulated target genes into the processes of proliferation, migration, invasion, and into key cascades of intracellular signaling and inflammatory processes. Conclusion. The findings suggest that the change in the microRNA expression in the ectopic endometrium and subsequent disruption of the regulation of the expression of their target genes is an important pathogenic link and may contribute to the development of endometriosis.Bobrov M.Yu., Balashov I.S., Filippova E.S., Almova I.K., Timofeeva A.V., Gusar V.A., Borovikov P.I., Khilkevich E.G., Chuprynin V.D., Pavlovich S.V.
Keywords
microRNA
endometriosis
expression of target genes
sequencing
polymerase chain reaction
References
1. Tosti C., Pinzauti S., Santulli P., Chapron C., Petraglia F. Pathogenetic mechanisms of deep infiltrating endometriosis. Reprod. Sci. 2015; 22(9): 1053-9.
2. Signorile P.G., Baldi A. New evidence in endometriosis. Int. J. Biochem. Cell Biol. 2015; 60: 19-22.
3. Harada T., ed. Endometriosis. Pathogenesis and treatment. Springer; 2014.
4. Fabian M.R., Sonenberg N., Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem. 2010; 79(1): 351-79.
5. Guo H., Ingolia N.T., Weissman J.S., Bartel D.P. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010; 466(7308): 835-40.
6. Lewis B.P., Shih I.H., Jones-Rhoades M.W., Bartel D.P., Burge C.B. Prediction of mammalian microRNA targets. Cell. 2003; 115(7): 787-98.
7. Bartel D.P. MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2): 215-33.
8. Kloosterman W.P., Plasterk R.H.A. The diverse functions of microRNAs in animal development and disease. Dev. Cell. 2006; 11(4): 441-50.
9. Takasaki S. Roles of microRNAs in cancers and development. Methods Mol. Biol. 2015; 1218: 375-413.
10. Ohlsson Teague E.M., Van der Hoek K.H., Van der Hoek M.B., Perry N., Wagaarachchi P., Robertson S.A. et al. MicroRNA-regulated pathways associated with endometriosis. Mol. Endocrinol. 2009; 23(2): 265-75.
11. Filigheddu N., Gregnanin I., Porporato P.E., Surico D., Perego B., Galli L. et al. Differential expression of micrornas between eutopic and ectopic endometrium in ovarian endometriosis. J. Biomed. Biotechnol. 2010; 2010: 369549.
12. 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.
13. Zhao M., Tang Q., Wu W., Xia Y., Chen D., Wang X. miR-20a contributes to endometriosis by regulating NTN4 expression. Mol. Biol. Rep. 2014; 41(9): 5793-7.
14. 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.
15. 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): 642-52.
16. 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.
17. Saare M., Rekker K., Laisk-Podar T., Sõritsa D., Roost A.M., 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.
18. 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.
Received 06.04.2018
Accepted 20.04.2018
About the Authors
Mikhail Y. Bobrov, Ph.D., Head of the Laboratory of molecular pathophysiology, National Medical Research Center of Obstetrics, Gynecology and Perinatology namedafter Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79032518677. E-mail: mbobr@mail.ru
Ivan S. Balashov, Junior Researcher, Laboratory of Bioinformatics, National Medical Research Center of Obstetrics, Gynecology and Perinatology named
after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: i_balashov@oparina4.ru
Elena S. Fillipova, obstetrician-gynecologist of the gynecological department, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4
Indira K. Almova, postgraduate student of the Surgery Department, National Medical Research Center of Obstetrics, Gynecology, and Perinatology named
after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79054357317. E-mail: www.gold11@mail.ru
Anzhelika V. Timofeeva, Ph.D., Senior Researcher, Laboratory of Molecular Pathophysiology, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: v_timofeeva@oparina4.ru
Vladislava A. Gusar, Ph.D., Senior Researcher, Laboratory of Molecular Pathophysiology, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: v_gusar@oparina4.ru
Pavel I. Borovikov, head of the Laboratory of Bioinformatics, National Medical Research Center of Obstetrics, Gynecology and Perinatology named
after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: p_borovikov@oparina4.ru
Elena G. Khilkevich, MD, obstetrician-gynecologist of the Surgery Department, National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387783. E-mail: e_khilkevich@oparina4.ru. ORCID ID: 0000-0001-8826-8439
Vladimir D. Chuprynin, PhD, Head of the Surgery Department, National Medical Research Center of Obstetrics, Gynecology, and Perinatology named
after Academician V.I. Kulakov, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954383575. E-mail: v_chuprynin@oparina4.ru
Stanislav V. Pavlovich, Ph.D., Associate Professor, Scientific Secretary of National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Ministry of Health of Russia; Professor of the Department of Obstetrics, Gynecology, Perinatology, and Reproductology,
Institute of Professional Education, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954382100. E-mail: st.pavlovich@mail.ru
For citations: Bobrov M.Yu., Balashov I.S., Filippova E.S., Almova I.K., Timofeeva A.V., Gusar V.A., Borovikov P.I., Khilkevich E.G., Chuprynin V.D., Pavlovich S.V. Assessment of microRNA expression in retrocervical endometriotic lesions.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (6): 55-61. (in Russian)
https://dx.doi.org/10.18565/aig.2018.6.55-61
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