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      Long non‐coding RNA PVT1, a novel biomarker for chronic obstructive pulmonary disease progression surveillance and acute exacerbation prediction potentially through interaction with microRNA‐146a

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          Abstract

          Objective

          This study aimed to investigate the abilities of long non‐coding RNA PVT1 (lnc‐PVT1) and microRNA‐146a (miR‐146a) in predicting chronic obstructive pulmonary disease (COPD) susceptibility and acute exacerbation risk, moreover, to explore the association of lnc‐PVT1 with disease severity, inflammation, and miR‐146a in patients with COPD.

          Methods

          A total of 80 acute exacerbation of COPD (AECOPD) patients, 80 stable COPD patients, and 80 healthy controls (HCs) were consecutively recruited. Peripheral blood samples of all participants were collected to isolate peripheral blood mononuclear cells (PBMCs), and serum: PBMCs were used to detect lnc‐PVT1 and miR‐146a by RT‐qPCR; serum was used to detect inflammatory cytokines by ELISA. Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage of COPD was assessed.

          Results

          Lnc‐PVT1 expression was highest in AECOPD patients, followed by stable COPD patients and HCs. Receiver operating characteristic curves disclosed that lnc‐PVT1 distinguished AECOPD patients and stable COPD patients from HCs, also distinguished AECOPD patients from stable COPD patients. In AECOPD patients and stable COPD patients, lnc‐PVT1 expression positively correlated with GOLD stage and levels of TNF‐α, IL‐6, IL‐8, and IL‐17. Moreover, lnc‐PVT1 was negatively correlated with miR‐146a. For miR‐146a, its expression was lowest in AECOPD patients, followed by stable COPD patients and HCs, and it predicted reduced COPD susceptibility and decreased acute exacerbation risk; meanwhile, it negatively correlated with GOLD stage and inflammatory cytokine levels in AECOPD patients and stable COPD patients.

          Conclusion

          Lnc‐PVT1 assists the disease management and acute exacerbation risk monitoring of COPD via interaction with miR‐146a.

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          Most cited references23

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          Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

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            LncRNA PVT1 regulates prostate cancer cell growth by inducing the methylation of miR‐146a

            Abstract Prostate cancer is the third most common causes of death from cancer in men. Our previous study demonstrated that lncRNA PVT1 was overexpressed and played an oncogenic role in the progression of prostate cancer. However, the molecular mechanism of modulating the prostate cancer tumorigenesis was still unknown. In this study, we aim to investigate the interaction between PVT1 and miR‐146a in prostate cancer and reveal the potential mechanism in prostate cancer carcinogenesis. The expression level of miR‐146a was assessed by quantitative RT‐PCR. The correlation analysis and methylation status analysis was made to confirm the interaction between PVT1 and miR‐146a. Biological function analysis was performed through gain‐of‐function and loss‐of‐function strategies. Our results showed that miR‐146a was downregulated and negatively correlated with PVT1 level in prostate cancer. PVT1 mediated miR‐146a expression by inducing the methylation of CpG Island in its promoter. miR‐146a overexpression eliminated the effects of PVT1 knockdown on prostate cancer cells. PVT1 regulated prostate cancer cell viability and apoptosis depending on miR‐146a. Our study suggested a regulatory relationship between lncRNA PVT1 and miR‐146a during the process of the prostate cancer tumorigenesis. PVT1 regulated prostate cancer cell viability and apoptosis depending on miR‐146a. It would contribute to the diagnosis, treatment and prognosis of prostate cancer.
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              Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle

              Background The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma. Methods Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to dexamethasone and FCS. mRNA and lncRNA expression was measured by using a microarray and quantitative real-time PCR. Bioinformatic analysis was used to examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small interfering RNAs, and the effect on ASMC phenotype was examined. Results The mRNA expression profile was significantly different between patient groups after exposure to dexamethasone and FCS, and these were associated with biological pathways that might be relevant to the pathogenesis of asthma, including cellular proliferation and pathways associated with glucocorticoid activity. We also observed a significant change in lncRNA expression, yet the expression of only one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive nonsevere asthma and increased in patients with corticosteroid-insensitive severe asthma. Subsequent targeting studies demonstrated the importance of this lncRNA in controlling both proliferation and IL-6 release in ASMCs from patients with severe asthma. Conclusions lncRNAs are associated with the aberrant phenotype observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in reducing airway remodeling in asthmatic patients.
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                Author and article information

                Contributors
                yuli641006@sina.com
                huke_rmhospital@163.com
                Journal
                J Clin Lab Anal
                J. Clin. Lab. Anal
                10.1002/(ISSN)1098-2825
                JCLA
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                0887-8013
                1098-2825
                27 April 2020
                August 2020
                : 34
                : 8 ( doiID: 10.1002/jcla.v34.8 )
                : e23346
                Affiliations
                [ 1 ] Division of Respiratory Disease Renmin Hospital of Wuhan University Wuhan China
                [ 2 ] Department of Critical Care Medicine The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology Wuhan China
                [ 3 ] Department of Endocrinology The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology Wuhan China
                Author notes
                [*] [* ] Correspondence

                Ke Hu, Division of Respiratory Disease, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan 430060, China.

                Email: huke_rmhospital@ 123456163.com

                Li Yu, Department of Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 26, Shengli Street, Jiang'an District, Wuhan 430014, China.

                Email: yuli641006@ 123456sina.com

                Author information
                http://orcid.org/0000-0003-1209-4254
                https://orcid.org/0000-0001-9862-7239
                Article
                JCLA23346
                10.1002/jcla.23346
                7439356
                32342557
                a0e13817-314b-414a-b715-a01d1fdfe782
                © 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ 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
                : 26 February 2020
                : 18 March 2020
                : 01 April 2020
                Page count
                Figures: 5, Tables: 1, Pages: 9, Words: 5025
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                August 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.7 mode:remove_FC converted:20.08.2020

                Clinical chemistry
                acute exacerbation risk,chronic obstructive pulmonary disease,disease severity,inflammation,long non‐coding rnapvt1,mirna‐146a

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