Endometriotic Mesenchymal Stem Cells Epigenetic Pathogenesis: Deregulation of miR-200b, miR-145, and let7b in A Functional Imbalanced Epigenetic Disease

Mashayekhi, Parisa; Noruzinia, Mehrdad; Zeinali, Sirous; Khodaverdi, Sepideh

doi:10.22074/cellj.2019.5903

Endometriotic Mesenchymal Stem Cells Epigenetic Pathogenesis: Deregulation of miR-200b, miR-145, and let7b in A Functional Imbalanced Epigenetic Disease

Document Type : Original Article

Authors

¹ Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

² Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

³ Endometriosis Research Center, Iran University of Medical Science, Tehran, Iran

10.22074/cellj.2019.5903

Abstract

Objective
Stem cell issue is a strong theory in endometriosis pathogenesis. It seems that endometriotic mesenchymal stem cells (MSCs) show different characteristics compared to the normal MSCs. Determined high proliferation and low differentiation/ decidualization potential of endometriotic MSCs could be accompanied by their microRNAs deregulation influencing their fate and function. In this study for the first time, we evaluated the expression of miR-200b, miR-145, and let7b in endometriotic compared to non-endometriotic MSCs. These microRNAs are involved in biological pathways related to proliferation and differentiation of stem cells. Their aberrant expressions can disturb the proliferation/ differentiation balance in stem cells, altering their function and causing various diseases, like endometriosis.
Materials and Methods
In this experimental study, MSCs were isolated from three endometriotic and three non- endometriotic eutopic endometrium, followed by their characterization and culture. Expression of miR-200b, miR-145, and let-7b was ultimately analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
Results
We found that the expression of miR-200b was up-regulated (P < 0/0001) whereas the expression of miR- 145 and let-7b was down-regulated (P < 0.0001) in endometriotic MSCs in comparison with non-endometriotic normal controls.
Conclusion
Proliferation and differentiation are important dynamic balanced biological processes, while in equillibrium, they determine a healthy stem cell fate. It seems that they are deregulated in endometriotic MSCs and change their function. miR-200b, miR-145, and let7b are deregulated during endometriosis and they have pivotal roles in the modulating proliferation and differentiation of stem cells. We found up-regulation of miR-200b and down-regulation of miR-145 and let-7b in endometriotic MSCs. These changes can increase self-renewal and migration, while decreasing differentiation of endometriotic MSCs. Our achievements emphasize previous findings on the importance of proliferation/ differentiation balance in MSCs and clarify the role of microRNAs as main players in faulty endometriotic stem cells development.

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