Whole blood sequencing reveals circulating microRNA associations with high-risk traits in non-ST-segment elevation acute coronary syndrome

Wang, Alice; Kwee, Lydia Coulter; Grass, Elizabeth; Neely, Megan L.; Gregory, Simon G.; Fox, Keith A.A.; Armstrong, Paul W.; White, Harvey D.; Ohman, E. Magnus; Roe, Matthew T.; Shah, Svati H.; Chan, Mark Y.

doi:10.1016/j.atherosclerosis.2017.03.041

Cited by 29 publications

(24 citation statements)

References 45 publications

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“… 28 Chronic heart failure was significantly associated with lower circulating levels of miR-126-5p. 29 Lack of miR-126-5p reduced endothelial cell proliferation by derepression of the Notch1 inhibitor delta-like 1 homolog (Dlk1). 30 Currently, we are unable to provide definitive proof that ciR-126 indeed sponges miR-126-5p.…”

Section: Discussionmentioning

confidence: 99%

The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

Kölling

Seeger

Haddad

et al. 2018

Kidney International Reports

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IntroductionCircular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They might have an impact on microRNA expression by their sponging activity. The detectability in blood of these RNA transcripts has been demonstrated in patients with cancer and cardiovascular disease. We tested the hypothesis that circulating circRNAs in blood of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy may also be dysregulated and associated with patient survival.MethodsWe performed a global circRNA expression analysis using RNA isolated from blood of patients with AKI as well as controls. This global screen revealed several dysregulated circRNAs in patients with AKI. Most highly increased circRNA-array−based transcripts as well as expression of the circRNA target miR-126-5p were confirmed in blood of 109 patients with AKI, 30 age-matched healthy controls, 25 critically ill non-AKI patients, and 20 patients on maintenance hemodialysis by quantitative real-time polymerase chain reaction.ResultsCirculating concentrations of 3 novel circRNAs were amplified in blood of patients with AKI and in controls. Circular RNA sponge of miR-126 (or ciRs-126) was most highly altered compared to healthy controls and disease controls (fold change of 52.1). ciRs-126 was shown to bioinformatically sponge miR-126-5p, which was found to be highly suppressed in AKI patients and hypoxic endothelial cells. Cox regression and Kaplan−Meier curve analysis revealed ciRs-126 as an independent predictor of 28-day survival (P < 0.01).ConclusionCirculating concentrations of circRNAs in patients with AKI are detectable. ciRs-126 may potentially sponge miR-126-5p and acts as a predictor of mortality in this patient cohort.

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Section: Discussionmentioning

confidence: 99%

The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

Kölling

Seeger

Haddad

et al. 2018

Kidney International Reports

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“…miR‐144‐5p, first discovered to be a potential biomarker of follicular thyroid cancer, may also be a regulatory factor in various disease, including metabolic disease (metabolic syndrome and diabetes), malignant tumour (non‐small‐cell lung cancer, breast cancer, bladder cancer, oesophageal carcinoma and gastric cancer), inflammatory diseases (tuberculosis, obesity and amyotrophic lateral sclerosis), Alzheimer's disease, depressive disorders and coronary syndrome . miR‐144‐5p inhibited antibacterial autophagy and the immune response to Mycobacterium tuberculosis via repressing DNA damage‐regulated autophagy modulator 2, which is a coordinator of antimicrobial autophagy …”

Section: Discussionmentioning

confidence: 99%

Assessment of microRNA‐144‐5p and its putative targets in inflamed gingiva from chronic periodontitis patients

Wang

Chen

et al. 2018

J of Periodontal Research

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Background and Objective This study aimed to discover the distinctive MicroRNAs (miRNA) functioning in the pathogenesis of periodontal inflammation, which might be potential therapy targets of chronic periodontitis. Material and Methods miRNA profiles of human inflamed gingival tissue from three previous microarrays were re‐analysed. Gingival tissues were collected for the validation of overlapping miRNAs, and a network was constructed to show regulatory connection between overlapping miRNAs and periodontitis‐associated target genes. Potential miRNAs were screened based on their expression levels and predicted target genes. Correlation analysis and binding site prediction were conducted to reveal the relationship between the potential miRNAs and their target genes. Results miR‐144‐5p, found to be upregulated in all three studies, showed the greatest upregulation (P < 0.0001). Another 16 miRNAs (10 upregulated and six downregulated) overlapped between any two of the three studies. All overlapping miRNAs had expected expression levels except for miR‐203 during validation. Ten miRNAs (six upregulated and four downregulated) were found to have periodontal inflammation‐associated targets. Cyclooxygenase 2 (COX2) and interleukin‐17F (IL17F), predicted target genes of upregulated miR‐144‐5p, showed significant decreases and were negatively correlated with miR‐144‐5p in the periodontitis group (r = −0.742 for COX2, r = −0.615 for IL17F). Conclusion This re‐analysis of miRNA signatures has implied the potential regulatory mechanism of miR‐144‐5p and its potential for exploring alternative therapeutic approaches, especially those that use miRNA delivery systems to treat chronic periodontitis. Nevertheless, further study based on larger sample size and homogenous cells is needed to reveal the exact roles of miRNAs in chronic periodontitis.

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“…Aligned reads were then mapped to primary miRNA transcripts from miRBase (v. 21, 2813 miRNAs) using bedtools (v. 2.21.0) 63,64 . MiR-486 was greatly enriched in the final mapped reads; we removed this miR from the final analysis set as this is a reported artifact of the Illumina library prep 65,66 . We retained 247 miRNAs for analysis that were expressed at a level of ≥1 rpm in at least 20 samples.…”

Section: Mirna Concentration Profiling Trilogy-acs Non-targeted Mirnmentioning

confidence: 99%

Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements

Becker

Kwee

Neely

et al. 2020

Sci Rep

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changes in platelet physiology are associated with simultaneous changes in microRnA concentrations, suggesting a role for microRnA in platelet regulation. Here we investigated potential associations between microRnA and platelet reactivity (pR), a marker of platelet function, in two cohorts following a non-St elevation acute coronary syndrome (nSte-AcS) event. first, non-targeted microRnA concentrations and pR were compared in a case (n = 77) control (N = 76) cohort within the larger TRILOGY-ACS trial. MicroRNA significant in this analysis plus CVD-associated microRNAs from the literature were then quantified by targeted rt-PCR in the complete TRILOGY-ACS cohort (N = 878) and compared with matched PR samples. Finally, microRNA significant in the non-targeted & targeted analyses were verified in an independent post NSTE-ACS cohort (N = 96). From the non-targeted analysis, 14 microRNAs were associated with PR (Fold Change: 0.91-1.27, p-value: 0.004-0.05). From the targeted analysis, five microRNAs were associated with PR (Beta: −0.09-0.22, p-value: 0.004-0.05). Of the 19 significant microRNAs, three, miR-15b-5p, miR-93 and miR-126, were consistently associated with pR in the tRiLoGY-AcS and independent Singapore post-AcS cohorts, suggesting the measurement of circulating microRnA concentrations may report on dynamic changes in platelet biology following a cardiovascular ischemic event.Despite advancements in its management, cardiovascular disease including non-ST elevation acute coronary syndrome (NSTE-ACS) remains a major cause of patient morbidity and mortality 1-4 . Antiplatelet therapies including P2Y 12 antagonists are used to treat NSTE-ACS acutely and in the longer-term. While measurements of platelet reactivity (PR) have facilitated the rapid quantification of anti-platelet medication efficacy, questions still remain about the utility of PR to predict clinical outcomes 5-8 . Platelet genetics and PR sub-studies from large-scale clinical trials have informed our understanding of individual variability in P2Y 12 inhibitor response, but genomic regulation of individual patient's PR has not been fully clarified 9-14 .Small non-coding ribonucleic acids (RNA) including microRNAs have emerged as potential regulators of PR in patients with cardiovascular disease 15 . MicroRNAs (miRNAs) are 18-22 nucleotide non-coding RNAs that play an essential role in gene modulation and expression and are established regulators of cardiovascular

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Whole blood sequencing reveals circulating microRNA associations with high-risk traits in non-ST-segment elevation acute coronary syndrome

Cited by 29 publications

References 45 publications

The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury

Assessment of microRNA‐144‐5p and its putative targets in inflamed gingiva from chronic periodontitis patients

Circulating MicroRNA Profiling in Non-ST Elevated Coronary Artery Syndrome Highlights Genomic Associations with Serial Platelet Reactivity Measurements

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