DNA methylation is involved in the microRNA-886-3p gene expression and plays a potential role in hematopoietic stem and progenitor cell mobilization through affecting SDF-1

Zamani, Homa ; Soleimani, Masoud ; Kaviani, Saeed ; Azimi, Amin ; Atashi, Amir

Abstract

The role of the sympathetic nervous system (SNS) in hematopoietic stem and progenitor cell (HSPC) mobilization has been largely investigated. However, there is a critical need for the identification of the underlying contributing factors to improve HSPC yield for transplantation. It has been demonstrated that miR-886-3p targets stromal-derived factor-1 (SDF-1), the central mediator of mobilization, and therefore may play a part in this process. Besides, miR-886-3p expression can be epigenetically regulated through DNA methylation modifications inits gene promoter. Here, to assess the contribution of miR-886-3p and other epigenetic factors in HSPC mobilization, human bone marrow-derived mesenchymal stem cells (MSCs) were treated with the β-adrenergic agonist of isoprenaline. The expression of miR-886-3p and SDF-1and the gene promoter methylation status of this miRNA were then respectively evaluated through the appropriate PCR techniques. As expected, despite a transient initial increase in SDF-1mRNA level, its expression reduced, and miR-886-3plevel remarkably increased 48 h following treatment. The gene promoter methylation pattern of miR-886-3p also changed from a full methylated state to a partially methylated one. Together, our findings suggest that miR-886-3p can be epigenetically regulated and through suppressing the expression of SDF-1 play an active role in the SNS-mediated HSPC mobilization.

Keyword(s)

Hematopoietic Stem and Progenitor Cell; Methylation; miR-886-3p; Mobilization; β-adrenergic agonist

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