z-logo
open-access-imgOpen Access
The 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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here