Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients

PLOS ONE, Dec 2019

Background microRNA (miRNA) belongs to the non-coding RNAs family responsible for the regulation of gene expression. Renalase is a protein composed of 342 amino acids, secreted by the kidneys and possibly plays an important role in the regulation of sympathetic tone and blood pressure. The aim of the present study was to investigate plasma renalase concentration, and explore the relationship between miRNA-146a-5p expression and plasma renalase levels in hemodialyzed patients. Methods The study population comprised 55 subjects who succumbed to various cardiac events, 27 women and 28 men, aged 65–70 years. The total RNA including miRNA fraction was isolated using QiagenmiRNEasy Serum/Plasma kit according to the manufacturer’s protocol. The isolated miRNAs were analyzed using a quantitative polymerase chain reaction (qRT-PCR) technique. The plasma renalase levels were measured using a commercial ELISA kit. Results In the group of patients with high levels of renalase, higher miRNA-146a expression was found, compared with those with low concentration of renalase. Patients with simultaneous low miRNA-146a expression and high level of renalase were confirmed to deliver a significantly longer survival time compared with other patients. Conclusions miRNA-146a and plasma renalase levels were estimated as independent prognostic factors of hemodialyzed patients’ survival time. Patients with low miRNA-146a expression demonstrated a significantly longer survival time in contrast to the patients with a high expression level of miRNA-146a. Moreover, a significantly longer survival time was found in patients with high renalase activity compared with patients with low activity of the enzyme.

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Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients

June Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients Marcin Dziedzic 0 1 Tomasz Powro zek 1 Ewelina Orøowska 1 Wojciech Koch 1 Wirginia Kukula-Koch 1 2 Kinga Gaweø 1 Anna Bednarek-Skublewska 1 Teresa Maøecka- Massalska 1 Janusz Milanowski 1 Beata Petkowicz 1 Janusz Solski 0 1 0 Department of Laboratory Diagnostic, Medical University of Lublin, Lublin, Poland, 2 Department of Human Physiology, Medical University of Lublin, Lublin, Poland, 3 Department of Nephrology, Medical University of Lublin, Lublin, Poland, 4 Chair and Department of Bromatology, Medical University of Lublin , Lublin , Poland 1 Editor: Julio Vera, Friedrich-Alexander-Universitat Erlangen-Nurnberg , GERMANY 2 Chair and Department of Pharmacognosy with Medicinal Plants Unit, Medical University of Lublin, Lublin, Poland, 6 Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Poland, 7 Department of Pneumonology , Oncology and Allergology , Medical University of Lublin, Lublin, Poland, 8 Department of Oral Medicine, Medical University of Lublin , Lublin , Poland - Background microRNA (miRNA) belongs to the non-coding RNAs family responsible for the regulation of gene expression. Renalase is a protein composed of 342 amino acids, secreted by the kidneys and possibly plays an important role in the regulation of sympathetic tone and blood pressure. The aim of the present study was to investigate plasma renalase concentration, and explore the relationship between miRNA-146a-5p expression and plasma renalase levels in hemodialyzed patients. Methods The study population comprised 55 subjects who succumbed to various cardiac events, 27 women and 28 men, aged 65±70 years. The total RNA including miRNA fraction was isolated using QiagenmiRNEasy Serum/Plasma kit according to the manufacturer's protocol. The isolated miRNAs were analyzed using a quantitative polymerase chain reaction (qRT-PCR) technique. The plasma renalase levels were measured using a commercial ELISA kit. Results In the group of patients with high levels of renalase, higher miRNA-146a expression was found, compared with those with low concentration of renalase. Patients with simultaneous low miRNA-146a expression and high level of renalase were confirmed to deliver a significantly longer survival time compared with other patients. Conclusions miRNA-146a and plasma renalase levels were estimated as independent prognostic factors of hemodialyzed patients' survival time. Patients with low miRNA-146a expression demonstrated a significantly longer survival time in contrast to the patients with a high expression level of miRNA-146a. Moreover, a significantly longer survival time was found in patients with high renalase activity compared with patients with low activity of the enzyme. Introduction microRNA (miRNA) belongs to the non-coding RNAs family. Current estimates suggest that more than 60% of human protein-coding genes are regulated by miRNAs [ 1 ]. mRNA is not just a simple messenger between the DNA and various proteins, but is responsible for the regulation of genome organization and gene expression post-transcriptionally, as a single miRNA can bind and consequently regulate the expression of more than 100 different transcripts. miRNAs may be able to regulate up to 30% of the protein-coding genes in the entire human genome. miRNAs recognize their targets based on the sequence complementarity [ 2 ]. In humans, miRNAs mainly inhibit protein translation of their target genes and only infrequently cause a degradation or a cleavage of mRNA itself [ 2 ]. Previous studies denote that miRNA is crucial in regulation of practically all functions of a cell, from the initial proliferation, through the differentiation of the cell and up to its apoptosis [ 3 ]. The above conclusions are proven by further observations, shedding light on the occurrence of various diseases such as inflammatory and cardiovascular (CVD) malfunctions, or even cancers and the consequence of the functional abnormalities in the miRNA regulatory system [ 4 ]. Moreover, miRNAs are easily accessible for their concentration measurements in the plasma, serum, or also in urine due to their very specific expression profiles. The determination of these molecular biomarkers in the biological material may significantly improve the diagnosis of the patients and bring more data on the pathological mechanisms and also individually. miRNA is suggested to be one of the main factors of the regulation of gene expression, which has an impact on both physiological cardiac development and many pathological processes including cardiac arrhythmia, hypertension, heart failure, cardiac fibrosis, coronary artery disease, and myocardial infarction [ 3 ]. The chronic kidney disease (CKD) has been widely known as a risk factor for cardiovascular diseases. The CKD patients were often diagnosed with CVD, and died before being directed t (...truncated)


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Marcin Dziedzic, Tomasz Powrózek, Ewelina Orłowska, Wojciech Koch, Wirginia Kukula-Koch, Kinga Gaweł, Anna Bednarek-Skublewska, Teresa Małecka-Massalska, Janusz Milanowski, Beata Petkowicz, Janusz Solski. Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients, PLOS ONE, 2017, Volume 12, Issue 6, DOI: 10.1371/journal.pone.0179218