Open AccessThe human rs1050286 polymorphism alters LOX ‐1 expression through modifying miR‐24 binding
Author(s) -
Morini Elena,
Rizzacasa Barbara,
Pucci Sabina,
Polidoro Chiara,
Ferrè Fabrizio,
Caporossi Daniela,
Helmer Citterich Manuela,
Novelli Giuseppe,
Amati Francesca
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12716
Subject(s) - snp , single nucleotide polymorphism , biology , three prime untranslated region , pathogenesis , microrna , untranslated region , microbiology and biotechnology , hela , allele , gene , genetics , messenger rna , genotype , cell , immunology
The up‐regulation of lectin‐like oxidized low‐density lipoprotein receptor‐1 ( LOX ‐1), encoded by the OLR 1 gene, plays a fundamental role in the pathogenesis of atherosclerosis. Moreover, OLR 1 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 OLR 1 , ‘naturally’ mutated by the presence of the rs1050286 single nucleotide polymorphism ( SNP ). Luciferase assays revealed that miR‐24 targets OLR 1 3′ UTR ‐G, but not 3′ UTR ‐A ( P < 0.0005). The functional relevance of miR‐24 in regulating the expression of OLR 1 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 OLR 1 both at RNA and protein level. Our results indicate that rs1050286 SNP significantly affects miR‐24 binding affinity to the 3′ UTR of OLR 1 , causing a more efficient post‐transcriptional gene repression in the presence of the G allele. On this basis, we considered that OLR 1 rs1050286 SNP may contribute to modify OLR 1 susceptibility to AMI and CAD , so ORL 1 SNP s screening could help to stratify patients risk.