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An Exonic Switch Regulates Differential Accession of microRNAs to the Cd34 Transcript in Atherosclerosis Progression

1
Department of Nephrology, Hospital Universitari Bellvitge and Bellvitge Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08907 Barcelona, Spain
2
Independent Researcher, Esplugues de Llobregat, 08950 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
Genes 2019, 10(1), 70; https://doi.org/10.3390/genes10010070
Received: 18 December 2018 / Revised: 7 January 2019 / Accepted: 14 January 2019 / Published: 21 January 2019
(This article belongs to the Special Issue microRNA in Health and Disease)
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Abstract

Background: CD34+ Endothelial Progenitor Cells (EPCs) play an important role in the recovery of injured endothelium and contribute to atherosclerosis (ATH) pathogenesis. Previously we described a potential atherogenic role for miR-125 that we aimed to confirm in this work. Methods: Microarray hybridization, TaqMan Low Density Array (TLDA) cards, qPCR, and immunohistochemistry (IHC) were used to analyze expression of the miRNAs, proteins and transcripts here studied. Results: Here we have demonstrated an increase of resident CD34-positive cells in the aortic tissue of human and mice during ATH progression, as well as the presence of clusters of CD34-positive cells in the intima and adventitia of human ATH aortas. We introduce miR-351, which share the seed sequence with miR-125, as a potential effector of CD34. We show a splicing event at an internal/cryptic splice site at exon 8 of the murine Cd34 gene (exonic-switch) that would regulate the differential accession of miRNAs (including miR-125) to the coding region or to the 3’UTR of Cd34. Conclusions: We introduce new potential mediators of ATH progression (CD34 cell-clusters, miR-351), and propose a new mechanism of miRNA action, linked to a cryptic splicing site in the target-host gene, that would regulate the differential accession of miRNAs to their cognate binding sites. View Full-Text
Keywords: atherosclerosis; miR-125b; CD34 cell-clusters; CD34 cryptic splicing; ORF miRNA target; exon switch atherosclerosis; miR-125b; CD34 cell-clusters; CD34 cryptic splicing; ORF miRNA target; exon switch
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Hueso, M.; Cruzado, J.M.; Torras, J.; Navarro, E. An Exonic Switch Regulates Differential Accession of microRNAs to the Cd34 Transcript in Atherosclerosis Progression. Genes 2019, 10, 70.

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