The possible origin of miRNAs differentially regulated in leiomyoma progenitors

Abstract

Background: Leiomyoma are the most common indication for hysterectomy in the world and have a strong economic impact on health care systems; many different mechanisms have been considered for their aetiology, such as inflammation, dysregulated progenitor cells or different regulation of miRNAs. After performing a whole genome miRNA profiling in progenitor cells (PCs) derived from healthy myometrium (MPCs) and from leyomioma (LPCs), only 15 miRNAs were identified as differentially expressed between MPCs and LPCs. Progenitor cells from Amniotic Fluid (AFPCs) are considered the most undifferentiated cells after the embryonic ones. Here we try to clarify if the miRNAs differently regulated between leiomyoma and myometrium cells arise as a conversion of MPCs along the differentiation process or if they may originate from a divergent cell commitment. To track the origin of the dysregulation, miRNA expression was analyzed in AFPCs (considered as surrogate for embryonic cells), MPCs and LPCs.MPCs, LPCs and AFPCs were isolated and subjected to whole genoma miRNA profiling; the expression of the 15 miRNAs previously identified as differentially regulated in MPCs and LPCs was compared to that detected in AFPCs.Results: Clustering analysis sub-grouped the 15 miRNAs into 4 major clusters that converge to the KEGG pathways: Adherens junction, ECM-receptor interaction, TGFβ signaling and cell cycle. miRNAs are differentially regulated in MPCs and LPCs compared to AFPCs and 10/15 of them show statistically significant variations between MPCs and LPCs.Conclusion(s): Our results seem to point that a linear physiological differentiation axis exists from AFPCS to MPCs that, under particular insults, pathologically continues toward LPCs.Our results seem to point that a linear physiological differentiation axis exists from AFPCS to MPCs that, under particular insults, pathologically continues toward LPCs.