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      Long noncoding RNA PVT1 contributes to vascular endothelial cell proliferation via inhibition of miR-190a-5p in diagnostic biomarker evaluation of chronic heart failure

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          Abstract

          Long noncoding RNAs (lncRNAs) and microRNAs (miRs) serve critical roles in various cellular processes and can be used as noninvasive biomarkers in human diseases. The present study aimed to investigate the effects of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-190a-5p on vascular endothelial cell (EC) proliferation and assess their clinical value in the diagnosis of chronic heart failure (CHF). The expression of PVT1 and miR-190a-5p was investigated using reverse transcription-quantitative PCR. The interaction between PVT1 and miR-190a-5p was confirmed using a luciferase reporter assay. A Cell Counting Kit-8 assay was performed to examine EC proliferation. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of PVT1 and miR-190a-5p. PVT1 directly decreased the expression of miR-190a-5p in ECs. Overexpression of miR-190a-5p in ECs led to inhibited cell proliferation and miR-190a-5p antagonized the promotive effect of PVT1 on EC proliferation. Serum expression of PVT1 increased, while serum expression of miR-190a-5p decreased in patients with CHF compared with healthy controls (all P<0.001). The ROC curves indicated that PVT1 and miR-190a-5p were two diagnostic biomarkers of CHF, and the combination of PVT1 and miR-190a-5p showed better diagnostic accuracy compared with using PVT1 or miR-190-5p alone. In conclusion, the present study demonstrated that PVT1 promoted EC proliferation by directly suppressing miR-190a-5p. Circulating PVT1 and miR-190a-5p are possible two candidate diagnostic biomarkers of CHF, and the combined detection of the two indicators may provide a novel approach for CHF diagnosis.

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          Identifying miRNAs, targets and functions

          microRNAs (miRNAs) are small endogenous non-coding RNAs that function as the universal specificity factors in post-transcriptional gene silencing. Discovering miRNAs, identifying their targets and further inferring miRNA functions have been a critical strategy for understanding normal biological processes of miRNAs and their roles in the development of disease. In this review, we focus on computational methods of inferring miRNA functions, including miRNA functional annotation and inferring miRNA regulatory modules, by integrating heterogeneous data sources. We also briefly introduce the research in miRNA discovery and miRNA-target identification with an emphasis on the challenges to computational biology.
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            Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer

            Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. The aim of our study was to illustrate the clinical significance of the lncRNA CRNDE-h in exosomes purified from the serum of patients with colorectal cancer (CRC). The study was divided into four parts: (1) The exosome isolated methods and lncRNA detected methods which accurately and reproducibly measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3) The origin of exosomal CRNDE-h was explorated in vitro and in vivo; (4) The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients. In pilot study, our results indicated that exosomal CRNDE-h was detectable and stable in serum of CRC patients, and derived from tumor cells. Then, the increased expression of exosomal CRNDE-h was successfully validated in 148 CRC patients when compared with colorectal benign disease patients and healthy donors. Exosomal CRNDE-h level significantly correlated with CRC regional lymph node metastasis (P = 0.019) and distant metastasis (P = 0.003). Moreover, at the cut-off value of 0.020 exosomal CRNDE-h level of serum, the area under ROC curve distinguishing CRC from colorectal benign disease patients and healthy donors was 0.892, with 70.3% sensitivity and 94.4% specificity, which was superior to carcinoembryogenic antigen. In addition, high exosomal CRNDE-h level has a lower overall survival rates than that for low groups (34.6% vs. 68.2%, P < 0.001). In conclusion, detection of lncRNA CRNDE-h in exosome shed a light on utilizing exosomal CRNDE-h as a noninvasive serum-based tumor marker for diagnosis and prognosis of CRC.
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              Pathophysiology of Heart Failure.

              Heart failure is considered an epidemic disease in the modern world affecting approximately 1% to 2% of adult population. It presents a multifactorial, systemic disease, in which--after cardiac injury--structural, neurohumoral, cellular, and molecular mechanisms are activated and act as a network to maintain physiological functioning. These coordinated, complex processes lead to excessive volume overload, increased sympathetic activity, circulation redistribution, and result in different, parallel developing clinical signs and symptoms. These signs and symptoms sum up to an unspecific clinical picture; thus invasive and noninvasive diagnostic tools are used to get an accurate diagnosis and to specify the underlying cause. The most important, outcome determining factor in heart failure is its constant progression. Constant optimizing of pharmatherapeutical regimes, novel targets, and fine regulation of these processes try to keep these compensatory mechanisms in a physiological range. Beside pharmacological therapy, interventional and surgical therapy options give new chances in the management of heart failure. For the optimization and establishment of these and novel therapeutical approaches, complete and comprehensive understanding of the underlying mechanisms is essentially needed. Besides diagnosis and treatment, efforts should be made for better prevention in heart failure by treatment of risk factors, or identifying and following risk groups. This summary of the pathophysiology of heart failure tries to give a compact overview of basic mechanisms and of the novel unfolding, progressive theory of heart failure to contribute to a more comprehensive knowledge of the disease.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                May 2020
                12 March 2020
                12 March 2020
                : 19
                : 5
                : 3348-3354
                Affiliations
                [1 ]Department of Emergency, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China
                [2 ]Department of Cardiovascular Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China
                [3 ]Department of Cardiovascular Medicine, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
                Author notes
                Correspondence to: Dr Shuguang Wang, Department of Cardiovascular Medicine, Weifang People's Hospital, 151 Guangwen Street, Weifang, Shandong 261000, P.R. China wang_dawn001@ 123456163.com
                Article
                ETM-0-0-8599
                10.3892/etm.2020.8599
                7132232
                32266032
                f9f51977-43da-4982-9b35-64373ad4b4af
                Copyright: © Sun et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 20 August 2019
                : 18 February 2020
                Categories
                Articles

                Medicine
                chronic heart failure,endothelial cell,long noncoding rna plasmacytoma variant translocation 1,microrna-190a-5p,proliferation,diagnosis

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