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      Long Noncoding RNAs CARMN, LUCAT1, SMILR, and MALAT1 in Thoracic Aortic Aneurysm: Validation of Biomarkers in Clinical Samples

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          Abstract

          Materials and Methods

          Relative expression of lncRNAs CARMN, LUCAT1, SMILR, and MALAT1 was tested in clinical aortic tissue and blood plasma samples from TAA and non-TAA patients using the qRT-PCR method. The Mann–Whitney U test was used to compare ΔCt values between the study groups. ROC curve analysis was performed to evaluate the diagnostic value of plasma lncRNAs.

          Results

          We found significantly reduced CARMN ( p = 0.033) and LUCAT1 ( p = 0.009) expression in aortic tissue samples from TAA patients. Relative expression of MALAT1 ( p = 0.117) and SMILR ( p = 0.610) did not differ in aortic tissue between the TAA and non-TAA groups. Expression of both LUCAT1 and SMILR was significantly decreased in TAA patients' blood plasma compared to controls ( p = 0.018 and p = 0.032, respectively). However, only LUCAT1 showed the ability to discriminate aneurysmal disease in patients' blood plasma (AUC = 0.654, 95%CI = 0.534‐0.775, p = 0.018).

          Conclusions

          We have shown that the expression of lncRNAs CARMN and LUCAT1 is reduced in dilated aortic tissue and that the LUCAT1 and SMILR expression is lower in the blood plasma of TAA patients. Decreased LUCAT1 expression in TAA patients' blood plasma may have diagnostic potential in discriminating patients with TAA.

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          Most cited references31

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges

            Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world. Although considerable progress has been made in the diagnosis, treatment and prognosis of CVD, there is still a critical need for novel diagnostic biomarkers and new therapeutic interventions to decrease the incidence of this disease. Recently, there is increasing evidence that circulating miRNAs (miRNAs), i.e. endogenous, stable, single-stranded, short, non-coding RNAs, can be used as diagnostic biomarkers for CVD. Furthermore, miRNAs represent potential novel therapeutic targets for several cardiovascular disorders. In this review we provides an overview of the effects of several CVD; including heart failure, acute myocardial infarction, arrhythmias and pulmonary hypertension; on levels of circulating miRNAs. In addition, the use of miRNA as therapeutic targets is also discussed, as well as challenges and recommendations in their use in the diagnosis of CVD.
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              CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis.

              Long noncoding RNAs (lncRNAs) are emerging as important regulators of developmental pathways. However, their roles in human cardiac precursor cell (CPC) remain unexplored. To characterize the long noncoding transcriptome during human CPC cardiac differentiation, we profiled the lncRNA transcriptome in CPCs isolated from the human fetal heart and identified 570 lncRNAs that were modulated during cardiac differentiation. Many of these were associated with active cardiac enhancer and super enhancers (SE) with their expression being correlated with proximal cardiac genes. One of the most upregulated lncRNAs was a SE-associated lncRNA that was named CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA. CARMEN exhibits RNA-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. Interestingly, CARMEN interacts with SUZ12 and EZH2, two components of the polycomb repressive complex 2 (PRC2). We demonstrate that CARMEN knockdown inhibits cardiac specification and differentiation in cardiac precursor cells independently of MIR-143 and -145 expression, two microRNAs located proximal to the enhancer sequences. Importantly, CARMEN expression was activated during pathological remodeling in the mouse and human hearts, and was necessary for maintaining cardiac identity in differentiated cardiomyocytes. This study demonstrates therefore that CARMEN is a crucial regulator of cardiac cell differentiation and homeostasis.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2020
                17 June 2020
                : 2020
                : 8521899
                Affiliations
                1Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėlių pr. 15, Kaunas LT-50103, Lithuania
                2Department of Cardiac, Thoracic and Vascular Surgery, Lithuanian University of Health Sciences, Eivenių g. 2, Kaunas LT-50161, Lithuania
                3Department of Cardiology, Lithuanian University of Health Sciences, Eivenių g. 2, Kaunas LT-50161, Lithuania
                Author notes

                Academic Editor: Zhongjie Shi

                Author information
                https://orcid.org/0000-0002-2270-1276
                https://orcid.org/0000-0001-5674-2490
                Article
                10.1155/2020/8521899
                7317319
                fb5c27bb-340b-4427-8760-66c19112f3c5
                Copyright © 2020 Vaiva Patamsytė et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 February 2020
                : 26 May 2020
                : 6 June 2020
                Funding
                Funded by: Lietuvos Mokslo Taryba
                Award ID: SEN-05/2016
                Categories
                Research Article

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