The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding

The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding

The up‐regulation of lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), encoded by the OLR1 gene, plays a fundamental role in the pathogenesis of atherosclerosis. Moreover, OLR1 polymorphisms were associated with increased susceptibility to acute myocardial infarction (AMI) and coronar...

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Main Authors: Morini, Elena, Rizzacasa, Barbara, Pucci, Sabina, Polidoro, Chiara, Ferrè, Fabrizio, Caporossi, Daniela, Helmer Citterich, Manuela, Novelli, Giuseppe, Amati, Francesca
Format: Online
Language:English
Published: John Wiley and Sons Inc. 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717858/
id pubmed-4717858
recordtype oai_dc
spelling pubmed-47178582016-01-26 The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding Morini, Elena Rizzacasa, Barbara Pucci, Sabina Polidoro, Chiara Ferrè, Fabrizio Caporossi, Daniela Helmer Citterich, Manuela Novelli, Giuseppe Amati, Francesca Short Communication The up‐regulation of lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), encoded by the OLR1 gene, plays a fundamental role in the pathogenesis of atherosclerosis. Moreover, OLR1 polymorphisms were associated with increased susceptibility to acute myocardial infarction (AMI) and coronary artery diseases (CAD). In these pathologies, the identification of therapeutic approaches that can inhibit or reduce LOX‐1 overexpression is crucial. Predictive analysis showed a putative hsa‐miR‐24 binding site in the 3′UTR of OLR1, ‘naturally’ mutated by the presence of the rs1050286 single nucleotide polymorphism (SNP). Luciferase assays revealed that miR‐24 targets OLR1 3′UTR‐G, but not 3′UTR‐A (P < 0.0005). The functional relevance of miR‐24 in regulating the expression of OLR1 was established by overexpressing miR‐24 in human cell lines heterozygous (A/G, HeLa) and homozygous (A/A, HepG2) for rs1050286 SNP. Accordingly, HeLa (A/G), but not HepG2 (A/A), showed a significant down‐regulation of OLR1 both at RNA and protein level. Our results indicate that rs1050286 SNP significantly affects miR‐24 binding affinity to the 3′UTR of OLR1, causing a more efficient post‐transcriptional gene repression in the presence of the G allele. On this basis, we considered that OLR1 rs1050286 SNP may contribute to modify OLR1 susceptibility to AMI and CAD, so ORL1 SNPs screening could help to stratify patients risk. John Wiley and Sons Inc. 2015-11-06 2016-01 /pmc/articles/PMC4717858/ /pubmed/26542080 http://dx.doi.org/10.1111/jcmm.12716 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Morini, Elena
Rizzacasa, Barbara
Pucci, Sabina
Polidoro, Chiara
Ferrè, Fabrizio
Caporossi, Daniela
Helmer Citterich, Manuela
Novelli, Giuseppe
Amati, Francesca
spellingShingle Morini, Elena
Rizzacasa, Barbara
Pucci, Sabina
Polidoro, Chiara
Ferrè, Fabrizio
Caporossi, Daniela
Helmer Citterich, Manuela
Novelli, Giuseppe
Amati, Francesca
The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding
author_facet Morini, Elena
Rizzacasa, Barbara
Pucci, Sabina
Polidoro, Chiara
Ferrè, Fabrizio
Caporossi, Daniela
Helmer Citterich, Manuela
Novelli, Giuseppe
Amati, Francesca
author_sort Morini, Elena
title The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding
title_short The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding
title_full The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding
title_fullStr The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding
title_full_unstemmed The human rs1050286 polymorphism alters LOX‐1 expression through modifying miR‐24 binding
title_sort human rs1050286 polymorphism alters lox‐1 expression through modifying mir‐24 binding
description The up‐regulation of lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), encoded by the OLR1 gene, plays a fundamental role in the pathogenesis of atherosclerosis. Moreover, OLR1 polymorphisms were associated with increased susceptibility to acute myocardial infarction (AMI) and coronary artery diseases (CAD). In these pathologies, the identification of therapeutic approaches that can inhibit or reduce LOX‐1 overexpression is crucial. Predictive analysis showed a putative hsa‐miR‐24 binding site in the 3′UTR of OLR1, ‘naturally’ mutated by the presence of the rs1050286 single nucleotide polymorphism (SNP). Luciferase assays revealed that miR‐24 targets OLR1 3′UTR‐G, but not 3′UTR‐A (P < 0.0005). The functional relevance of miR‐24 in regulating the expression of OLR1 was established by overexpressing miR‐24 in human cell lines heterozygous (A/G, HeLa) and homozygous (A/A, HepG2) for rs1050286 SNP. Accordingly, HeLa (A/G), but not HepG2 (A/A), showed a significant down‐regulation of OLR1 both at RNA and protein level. Our results indicate that rs1050286 SNP significantly affects miR‐24 binding affinity to the 3′UTR of OLR1, causing a more efficient post‐transcriptional gene repression in the presence of the G allele. On this basis, we considered that OLR1 rs1050286 SNP may contribute to modify OLR1 susceptibility to AMI and CAD, so ORL1 SNPs screening could help to stratify patients risk.
publisher John Wiley and Sons Inc.
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717858/
_version_ 1613525481760489472

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