MicroRNAs: Marcadores séricos en diabetes mellitus tipo 2 y ejercicio físico

Gómez-Banoy, Nicolás; Mockus, Ismena

doi:10.4067/s0034-98872016000300011

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…In addition, miRNAs are also known to be actively or passively released in circulation as intercellular communication molecules [42, 43]. To determine whether circulating miRNAs play a role in regulating the physiological function of ECFCs in PB, total RNA harvested from plasma of both HLTY individuals and CAD patients were purified and used for smRNA-seq.…”

Section: Resultsmentioning

confidence: 99%

Dysregulation of endothelial colony-forming cell function by a negative feedback loop of circulating miR-146a and -146b in cardiovascular disease patients

Chang

Tsai

Huang³

et al. 2017

PLoS ONE

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Functional impairment of endothelial colony-forming cells (ECFCs), a specific cell lineage of endothelial progenitor cells (EPCs) is highly associated with the severity of coronary artery disease (CAD), the most common type of cardiovascular disease (CVD). Emerging evidence show that circulating microRNAs (miRNAs) in CAD patients’ body fluid hold a great potential as biomarkers. However, our knowledge of the role of circulating miRNA in regulating the function of ECFCs and the progression of CAD is still in its infancy. We showed that when ECFCs from healthy volunteers were incubated with conditioned medium or purified exosomes of cultured CAD ECFCs, the secretory factors from CAD ECFCs dysregulated migration and tube formation ability of healthy ECFCs. It is known that exosomes influence the physiology of recipient cells by introducing RNAs including miRNAs. By using small RNA sequencing (smRNA-seq), we deciphered the circulating miRNome in the plasma of healthy individual and CAD patients, and found that the plasma miRNA spectrum from CAD patients was significantly different from that of healthy control. Interestingly, smRNA-seq of both healthy and CAD ECFCs showed that twelve miRNAs that had a higher expression in the plasma of CAD patients also showed higher expression in CAD ECFCs when compared with healthy control. This result suggests that these miRNAs may be involved in the regulation of ECFC functions. For identification of potential mRNA targets of the differentially expressed miRNA in CAD patients, cDNA microarray analysis was performed to identify the angiogenesis-related genes that were down-regulated in CAD ECFCs and Pearson’s correlation were used to identify miRNAs that were negatively correlated with the identified angiogenesis-related genes. RT-qPCR analysis of the five miRNAs that negatively correlated with the down-regulated angiogenesis-related genes in plasma and ECFC of CAD patients showed miR-146a-5p and miR-146b-5p up-regulation compared to healthy control. Knockdown of miR-146a-5p or miR-146b-5p in CAD ECFCs enhanced migration and tube formation activity in diseased ECFCs. Contrarily, overexpression of miR-146a-5p or miR-146b-5p in healthy ECFC repressed migration and tube formation in ECFCs. TargetScan analysis showed that miR-146a-5p and miR-146b-5p target many of the angiogenesis-related genes that were down-regulated in CAD ECFCs. Knockdown of miR-146a-5p or miR-146b-5p restores CAV1 and RHOJ levels in CAD ECFCs. Reporter assays confirmed the direct binding and repression of miR-146a-5p and miR-146b-5p to the 3’-UTR of mRNA of RHOJ, a positive regulator of angiogenic potential in endothelial cells. Consistently, RHOJ knockdown inhibited the migration and tube formation ability in ECFCs. Collectively, we discovered the dysregulation of miR-146a-5p/RHOJ and miR-146b-5p/RHOJ axis in the plasma and ECFCs of CAD patients that could be used as biomarkers or therapeutic targets for CAD and other angiogenesis-related diseases.

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Section: Resultsmentioning

confidence: 99%

Dysregulation of endothelial colony-forming cell function by a negative feedback loop of circulating miR-146a and -146b in cardiovascular disease patients

Chang

Tsai

Huang³

et al. 2017

PLoS ONE

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“…MiRNAs play key roles in many physiological and pathological processes, including tumorigenesis, proliferation, hematopoiesis, metabolism, immune function, epigenetics, and neurodegenerative diseases (Miska, 2005 ; O'Connell et al, 2010 ). SNP in miRNAs correlated closely with traditional risk factors of IS, such as atherosclerosis, hypertension, diabetes and hyperlipidemia (high cholesterol) (Boucherat et al, 2015 ; Li et al, 2015 ; Gómez-Banoy and Mockus, 2016 ; Schober and Weber, 2016 ). The four miRNAs we focused on—miR-146a, miR-149, miR-196a2, and miR-499—are intimately related to regulation of TNF-α (El Gazzar et al, 2011 ), MTHFR (Wu et al, 2013 ), annexin A1 (ANXA1) (Luthra et al, 2008 ), and CRP (Yang et al, 2012 ) respectively, which were general causes of cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

Association Between MicroRNAs Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis in Chinese Individuals

Weng

Zheng

et al. 2018

Front. Aging Neurosci.

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Objective: Previous studies have demonstrated that some single-nucleotide polymorphisms (SNPs) in miRNAs are related to the risk of ischemic stroke (IS), but the conclusions are still controversial and inconclusive. We performed this meta-analysis to further assess the association between miR-146a C>G (rs2910164), miR-149 T>C (rs2292832), miR-196a2 T>C (rs11614913), miR-499 A>G (rs3746444) and risk of IS in Chinese individuals.Methods: Relevant studies were identified in the databases of PubMed, Embase. The strength of correlation between microRNAs polymorphisms and IS risk was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models.Results: 5 studies, containing 2,632 cases and 3,191 controls, were included in this meta-analysis. The overall results of meta-analysis indicated that there were no significant association between miR-146a C>G (rs2910164), miR-149 T>C (rs2292832), miR-196a2 T>C (rs11614913), and the IS risk in the overall analyses. MiR-499 A>G (rs3746444) was associated with an increased IS risk under allele model (OR = 1.30, 95% CI = 1.02–1.66), heterozygous model (OR = 1.35, 95% CI = 1.01–1.79) and dominant model (OR = 1.36, 95% CI = 1.02–1.80) in Chinese. The sensitivity analysis results of these four polymorphisms were similar to the overall results.Conclusion: MiR-499 A>G (rs3746444) G allele and AG, AG + AA genotype might be risk factors of IS in Chinese. No significant association was observed between miR-146a C>G (rs2910164), miR-149 T>C (rs2292832), miR-196a2 T>C (rs11614913), and IS risk. The associations may be different due to geographical factors of China. More explorations in more diverse geographically regions with large sample size are expected to further verify the findings in the future.

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“…SNP existing in pre-miRNAs or genetic mutations can affect the expression of mature miRNAs or cause mutative expression [ 35 ]. SNP existing in miRNAs are closely related to traditional risk factors for IS, such as atherosclerosis, hypertension, hyperlipidemia (high cholesterol), and diabetes [ 36 – 39 ]. Based on preliminary studies, four miRNAs were selected [ miR-146aC>G (rs2910164), m iR-149T>C (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444] to investigate the genetic susceptibility of SNP and IS in the population of Southwest region of Guangxi in China.…”

Section: Discussionmentioning

confidence: 99%

Association of miR-146a, miR-149, miR-196a2, miR-499 gene polymorphisms with ischemic stroke in a Chinese people

Luo

Wang

et al. 2017

Oncotarget

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This study aimed to investigate genetic polymorphisms of miR-146a, miR-149, miR-196a2, and miR-499 and genetic susceptibility of ischemic stroke in the population of Guangxi in China. A case–control study was used to investigate miRNAs genetic polymorphisms in 298 patients with ischemic stroke and 303 healthy controls. Single-base extension polymerase chain reaction genotyping principle was used to detect genetic polymorphisms of miRNAs,and the relationship of genotype in each group and blood lipid was compared and analyzed. The genetic polymorphism of miR-499A>G (rs3746444) was associated with ischemic stroke (P < 0.05), and the risk of ischemic stroke was high in patients with G allele (OR = 1.455; 95% CI = 0.531–2.381; P = 0.039) and AG (OR = 1.339; 95% CI = 1.126–1.967; P = 0.037) genotype. The levels of low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, homocysteine, and lipoprotein in the ischemic stroke group were higher than those in the control group (P < 0.05). The genetic polymorphism of miR-499A>G (rs3746444) was related to ischemic stroke, and G allele and AG genotype may increase the risk of ischemic stroke in the population of Guangxi in China.

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MicroRNAs: Marcadores séricos en diabetes mellitus tipo 2 y ejercicio físico

Abstract: MicroRNAs: Marcadores séricos en diabetes mellitus tipo 2 y ejercicio físicoNicolás Gómez-BaNoy 1,a , ismeNa mockus 1,b MicroRNAs: circulating biomarkers in type 2 Diabetes Mellitus and physical exercise (Rev Med Chile 2016; 144: 355-363)

Cited by 4 publications

References 46 publications

Dysregulation of endothelial colony-forming cell function by a negative feedback loop of circulating miR-146a and -146b in cardiovascular disease patients

Dysregulation of endothelial colony-forming cell function by a negative feedback loop of circulating miR-146a and -146b in cardiovascular disease patients

Association Between MicroRNAs Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis in Chinese Individuals

Association of miR-146a, miR-149, miR-196a2, miR-499 gene polymorphisms with ischemic stroke in a Chinese people

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