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


Parisa Mashayekhi, M.D, 1Mehrdad Noruzinia, M.D., Ph.D., 1,*Sirous Zeinali, Ph.D, 2Sepideh Khodaverdi, M.D, 3
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
Endometriosis Research Center, Iran University of Medical Science, Tehran, Iran
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
Endometriosis Research Center, Iran University of Medical Science, Tehran, Iran
*Corresponding Address: P.O.Box: 14115-111 Department of Medical Genetics Faculty of Medical Sciences Tarbiat Modares University Tehran Iran Email:noruzinia@modares.ac.ir
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Mashayekhi Parisa, Noruzinia Mehrdad, Zeinali Sirous, Khodaverdi Sepideh. Endometriotic Mesenchymal Stem Cells Epigenetic Pathogenesis: Deregulation of miR-200b, miR-145, and let7b in A Functional Imbalanced Epigenetic Disease. Cell J. 2019; 21(2): 179-185.

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.