Endometriotic Mesenchymal Stem Cells Epigenetic Pathogenesis: Deregulation Of MiR-200b, MiR-145, And Let7b In A Functional Imbalanced Epigenetic Disease

• Main Authors: Parisa Mashayekhi, Mehrdad Noruzinia, Sirous Zeinali, Sepideh Khodaverdi
• Format: Article
• Language: English
• Published: Royan Institute (ACECR), Tehran 2019-02-01
• Series: Cell Journal
• Subjects: Cell Differentiation; Cell Self-Renewal; Mesenchymal Stromal Cells; microRNAs
• Online Access: https://celljournal.org/journal/article/abstract/5903

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.