Dataset Information

Rs41291957 controls miR-143 and miR-145 expression and impacts coronary artery disease risk.

ABSTRACT: The role of single nucleotide polymorphisms (SNPs) in the etiopathogenesis of cardiovascular diseases is well known. The effect of SNPs on disease predisposition has been established not only for protein coding genes but also for genes encoding microRNAs (miRNAs). The miR-143/145 cluster is smooth muscle cell-specific and implicated in the pathogenesis of atherosclerosis. Whether SNPs within the genomic sequence of the miR-143/145 cluster are involved in cardiovascular disease development is not known. We thus searched annotated sequence databases for possible SNPs associated with miR-143/145. We identified one SNP, rs41291957 (G > A), located -91 bp from the mature miR-143 sequence, as the nearest genetic variation to this miRNA cluster, with a minor allele frequency > 10%. In silico and in vitro approaches determined that rs41291957 (A) upregulates miR-143 and miR-145, modulating phenotypic switching of vascular smooth cells towards a differentiated/contractile phenotype. Finally, we analysed association between rs41291957 and CAD in two cohorts of patients, finding that the SNP was a protective factor. In conclusion, our study links a genetic variation to a pathological outcome through involvement of miRNAs.

SUBMITTER: Hall IF

PROVIDER: S-EPMC8495461 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

rs41291957 controls miR-143 and miR-145 expression and impacts coronary artery disease risk.

Hall Ignacio Fernando IF Climent Montserrat M Viviani Anselmi Chiara C Papa Laura L Tragante Vinicius V Lambroia Luca L Farina Floriana Maria FM Kleber Marcus E ME März Winfried W Biguori Carlo C Condorelli Gianluigi G Elia Leonardo L

EMBO molecular medicine 20210922 10

The role of single nucleotide polymorphisms (SNPs) in the etiopathogenesis of cardiovascular diseases is well known. The effect of SNPs on disease predisposition has been established not only for protein coding genes but also for genes encoding microRNAs (miRNAs). The miR-143/145 cluster is smooth muscle cell-specific and implicated in the pathogenesis of atherosclerosis. Whether SNPs within the genomic sequence of the miR-143/145 cluster are involved in cardiovascular disease development is not ...[more]

PMID: 34551209

Similar Datasets

Project description:BackgroundGlioblastoma multiforme (GBM) is the most common primary central nervous system malignancy and its unique invasiveness renders it difficult to treat. This invasive phenotype, like other cellular processes, may be controlled in part by microRNAs - a class of small non-coding RNAs that act by altering the expression of targeted messenger RNAs. In this report, we demonstrate a straightforward method for creating invasive subpopulations of glioblastoma cells (IM3 cells). To understand the correlation between the expression of miRNAs and the invasion, we fully profiled 1263 miRNAs on six different cell lines and two miRNAs, miR-143 and miR-145, were selected for validation of their biological properties contributing to invasion. Further, we investigated an ensemble effect of both miR-143 and miR-145 in promoting invasion.MethodsBy repeated serial invasion through Matrigel®-coated membranes, we isolated highly invasive subpopulations of glioma cell lines. Phenotypic characterization of these cells included in vitro assays for proliferation, attachment, and invasion. Micro-RNA expression was compared using miRCURY arrays (Exiqon). In situ hybridization allowed visualization of the regional expression of miR-143 and miR-145 in tumor samples, and antisense probes were used investigate in vitro phenotypic changes seen with knockdown in their expression.ResultsThe phenotype we created in these selected cells proved stable over multiple passages, and their microRNA expression profiles were measurably different. We found that two specific microRNAs expressed from the same genetic locus, miR-143 and miR-145, were over-expressed in our invasive subpopulations. Further, we also found that combinatorial treatment of these cells with both antisense-miRNAs (antimiR-143 and -145) will abrogated their invasion without decreasing cell attachment or proliferation.ConclusionsTo best of our knowledge, these data demonstrate for the first time that miR-143 and miR-145 regulate the invasion of glioblastoma and that miR-143 and -145 could be potential therapeutic target for anti-invasion therapies of glioblastoma patients.

Project description:BackgroundAn elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients.MethodsA total of 100 participants were enrolled and included normal control subjects (NC = 20), hyperhomocysteinaemia alone subjects (Hhcy = 25), hyperhomocysteinaemia and carotid artery atherosclerosis combined subjects (Hhcy + ATH = 30) and patients with standalone carotid artery atherosclerosis (ATH = 25). Plasma Hcy, supplementary biochemical parameters and carotid artery ultrasonography (USG) were measured in all participants. MicroRNA expression levels in the peripheral blood were calculated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The correlations of miR-143 and miR-145 with Hcy, blood lipid parameters and carotid artery atherosclerotic plaques were evaluated using Pearson's correlation coefficients. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the capacities of miR-143 and miR-145 for the detection of Hhcy and atherosclerosis patients.ResultsMiR-143 and miR-145 exhibited trends towards significance with stepwise decreases from the NC to Hhcy groups and then to the Hhcy + ATH and ATH groups. Similar results were observed in the carotid artery plaque group (Hhcy + ATH and ATH grups) compared with the no-plaque group (NC and Hhcy groups). The miR-143 expression level exhibited significant negative correlations with Hcy, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). The miR-145 expression level exhibited significant negative correlations with Hcy, TC, triglyceride (TG) and LDL-c. MiR-143 and miR-145 exhibited the greatest area under the curves (AUCs) (0.775 and 0.681, respectively) for the detection of every Hhcy patient, including those in the Hhcy and Hhcy + ATH groups, from among all subjects.ConclusionThe results indicated that the levels of atherosclerosis-associated circulating miR-143 and miR-145 are linked to Hhcy. MiR-143 may be used as a potential non-invasive biomarkers of Hhcy and thus may be helpful in predicting the progress of atherosclerosis in Hhcy patients.

Dataset Information

Rs41291957 controls miR-143 and miR-145 expression and impacts coronary artery disease risk.

Publications

rs41291957 controls miR-143 and miR-145 expression and impacts coronary artery disease risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets