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Identification of miR-17, miR-21, miR-27a, miR-106b and miR-222 as endoplasmic reticulum stress-related potential biomarkers in circulation of patients with atherosclerosis

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Abstract

Atherosclerosis and related cardiovascular diseases are among the most common causes of death worldwide. Unfolded protein response, also known as Endoplasmic reticulum stress, has a critical role in many diseases including atherosclerosis. Small non-coding microRNAs (miRNA), which generally suppress gene expression, regulate UPR signalling and they may also be involved in the progression of atherosclerosis. We aim to investigate the expression levels of miR-17, miR-21, miR-27a, miR-106b, miR-222 and CHOP gene in circulation of atherosclerosis patients compared to healthy controls to establish a link between ER stress and atherosclerosis. miRNA containing whole RNA was isolated from blood samples of 25 patients with atherosclerosis and 26 healthy controls. Expression levels of miRNAs and CHOP were measured via Real Time PCR method. miR-17 and miR-106b were significantly increased while miR-21, miR-27a, and miR-222 were significantly decreased in patients compared to controls. CHOP gene was also dramatically and significantly induced in patient samples. miR-17, miR-21, miR-27a, miR-106b, miR-222 and CHOP were significantly differentially expressed in patients with atherosclerosis. Each miRNA and CHOP might regulate atherosclerotic plaque progression and they can be used as a biomarker in the diagnosis and follow-up of atherosclerosis-related cardiovascular diseases.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request without sharing patients’ information.

Abbreviations

ATF6:

Activating transcription factor 6

CAD:

Coronary artery disease

CHOP:

CCAAT-enhancer-binding protein homologous protein

CVDs:

Cardiovascular diseases

ER:

Endoplasmic reticulum

EPCs:

Endothelial progenitor cells

HMGCR:

Hydroxy-3-methylglutaryl- coenzyme A reductase gene

IRE1:

Inositol-requiring enzyme 1

IMA:

Internal mammary arteries

LPL:

Lipoprotein lipase

LDL-C:

Low-density lipoprotein cholesterol

LDL-R:

Low-density lipoprotein receptor

miRNAs:

MicroRNAs

PERK:

Protein kinase RNA-like endoplasmic reticulum kinase

UPR:

Unfolded protein response

UA:

Unstable angina

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Funding

This work was supported by the Scientific Research Projects Coordination Unit of Yuksek Ihtisas University under Grant Number 2018/01.001.

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  1. Department of Medical Biology, Faculty of Medicine, Yuksek Ihtisas University, Ankara, Turkey

    Pelin Telkoparan-Akillilar & Dilek Cevik

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  1. Pelin Telkoparan-Akillilar
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Contributions

Design and implementation of the research: PTA and DC. Performed the experiments: PTA and DC. Analysed the data: PTA and DC. Wrote the paper: PTA and DC. Both authors have read and approved the final version of the manuscript and they have met the criteria for authorship.

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Correspondence to Pelin Telkoparan-Akillilar.

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Telkoparan-Akillilar, P., Cevik, D. Identification of miR-17, miR-21, miR-27a, miR-106b and miR-222 as endoplasmic reticulum stress-related potential biomarkers in circulation of patients with atherosclerosis. Mol Biol Rep 48, 3503–3513 (2021). https://doi.org/10.1007/s11033-021-06352-7

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