Integrated analysis of miRNA and mRNA gene expression microarrays: Influence on platelet reactivity, clopidogrel response and drug-induced toxicity

Freitas, Renata Caroline Costa de; Bortolin, Raul Hernandes; Lopes, Mariana Borges Sodré; Hirata, Mário Hiroyuki; Hirata, Rosário Dominguez Crespo; Silbiger, Vivian Nogueira; Luchessi, André Ducati

doi:10.1016/j.gene.2016.08.028

Cited by 26 publications

(17 citation statements)

References 44 publications

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“…Between the TRILOGY-ACS and Singapore cohorts one miRNA, miR-15b-5p, was found to be both strand specific (either 3p or 5p, denoting the complementary mRNA strand the miRNA binds to and inhibits) and directionally consistent (miRNA concentration associated with increased or decreased PR) across both. These results are consistent with previous data suggesting miR-15b-5p modulates PR by targeting SENP5, a SUMO isopeptidase that is activated in the context of platelet activation, ischemia-reperfusion injury and cardiomyopathy [24][25][26] .…”

Section: Discussionsupporting

confidence: 93%

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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Section: Discussionsupporting

confidence: 93%

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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“…In addition, levels of platelet miRNAs in the circulation are associated with the risk for cardiovascular diseases, suggesting that platelet-derived miRNAs might have important roles as biomarkers of cardiovascular disease susceptibility, prognosis, or treatment [7]. An in silico study suggested that differential expression of miRNAs in platelets and their target mRNAs in peripheral blood cells might be associated with variability in platelet reactivity, drug response, and drug-induced toxicity [21]. …”

Section: Platelets Mirna Involved In Afmentioning

confidence: 99%

Circulating MicroRNAs as Potential Biomarkers of Atrial Fibrillation

Silva

Araújo

Freitas

et al. 2017

BioMed Research International

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Atrial fibrillation (AF) is the most common supraventricular arrhythmia in the population. MicroRNAs (small endogenous noncoding RNAs) are attractive candidates as biomarkers for AF, especially considering that miRNAs are stable and are detected within easily accessible biofluids such as blood. In this review, we selected twelve studies (2012 to 2016) that were classified according to the sample type. We aimed to provide an overview of the role of circulating miRNAs in AF and to discuss the variability of the results, seeking to improve the perspective of the use of miRNAs as potential noninvasive biomarkers for this heart disease.

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“…However, extensive studies are needed to explore the participation of miR-4701-3p and miR-4793-3p in the regulation of SHU00238 on CRC tumor in animals and human (Liang et al, 2017). MiR-4701-3p, derived from exosomes, was shown to influence clopidogrel-induced liver injury, platelet reactivity, and drug-induced toxicity (Freitas et al, 2016;de Freitas et al, 2017). MiR-4701-3p was downregulated in patients with high risk of cadiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

“…CFD has a role in coronary heart disease. (Freitas et al, 2016). But miR-4701-3p has not been identified in cancer especially in CRC.…”

Section: Discussionmentioning

confidence: 99%

SHU00238 Promotes Colorectal Cancer Cell Apoptosis Through miR-4701-3p and miR-4793-3p

Wang

Lin

et al. 2020

Front. Genet.

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Colorectal cancer is one of the most leading causes of death. Searching for new therapeutic targets for colorectal cancer is urgently needed. SHU00238, an isoxazole derivative, was reported to suppress colorectal tumor growth through microRNAs. But the underlying mechanisms still remain unknown. Here, we explored the mechanism of SHU00238 on colorectal cancer by RT-PCR, CCK-8, flow cytometry, mirTarBase, and GO enrichment analysis. We screened partial microRNAs regulated by SHU00238 in colorectal cancer cells. Furthermore, we identified that miR-4701-3p and miR-4793-3p can reverse the acceleration of SHU00238 on colorectal cancer cell apoptosis in HCT116 Cells. Finally, we found that SMARCA5, MBD3, VPS53, EHD4 are estimated to mediate the regulation of miR-4701-3p and miR-4793-3p on colorectal cancer cell apoptosis, which targets ATP-dependent chromatin remodeling pathway and endocytic recycling pathway. Taken together, our study reveals that SHU00238 promotes colorectal cancer cell apoptosis through miR-4701-3p and miR-4793-3p, which provide a potential drug target and therapeutic strategy for colorectal cancer.

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Integrated analysis of miRNA and mRNA gene expression microarrays: Influence on platelet reactivity, clopidogrel response and drug-induced toxicity

Cited by 26 publications

References 44 publications

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

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

Circulating MicroRNAs as Potential Biomarkers of Atrial Fibrillation

SHU00238 Promotes Colorectal Cancer Cell Apoptosis Through miR-4701-3p and miR-4793-3p

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