The Role of Non-coding RNAs in Viral Myocarditis

Zhang, Cong; Xiong, Yan; Zeng, Lijin; Peng, Zhihua; Liu, Zhihao; Zhan, Hong; Yang, Zhen

doi:10.3389/fcimb.2020.00312

Cited by 22 publications

(12 citation statements)

References 161 publications

(184 reference statements)

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“…Non-coding RNAs (ncRNAs) are a class of non-coding ribonucleic acids that are critical contributors to various biological processes, among which long non-coding RNAs (lncRNAs) spanning more than 200 nucleotides in length are the major members ( Batista and Chang, 2013 ). Our group and others have revealed that lncRNAs could regulate the occurrence and development of viral infection and that circulating non-coding RNAs might have a great value in the diagnosis of myocarditis ( Chen et al., 2018 ; Nie et al., 2020 ; Zhang C et al., 2020 ). Meanwhile, the roles of lncRNAs in myocarditis have attracted increasing attention ( Zhang et al., 2019 ; Xue et al., 2020 ; Zhang Y et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis

Nie

Wang

et al. 2021

Front. Cell. Infect. Microbiol.

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AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.

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Section: Introductionmentioning

confidence: 99%

Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis

Nie

Wang

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Regarding the latter scenario, viruses can hijack various ncRNAs to modulate the expression of both cellular and viral genes to establish an environment conducive to its own replication [ 38 ]. By contrast, certain dysregulated ncRNAs can also directly or indirectly affect viral replication and even directly target viral genomes [ 38 , 39 ]. Some reported observations of these phenomena, particularly involving the activity of miRNAs, are as follows.…”

Section: Known Impacts Of Ncrnas On Ev Replicationmentioning

confidence: 99%

Essential Role of Non-Coding RNAs in Enterovirus Infection: From Basic Mechanisms to Clinical Prospects

Zhu

Chen

Zhang

et al. 2021

IJMS

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Enteroviruses (EVs) are common RNA viruses that can cause various types of human diseases and conditions such as hand, foot, and mouth disease (HFMD), myocarditis, meningitis, sepsis, and respiratory disorders. Although EV infections in most patients are generally mild and self-limiting, a small number of young children can develop serious complications such as encephalitis, acute flaccid paralysis, myocarditis, and cardiorespiratory failure, resulting in fatalities. Established evidence has suggested that certain non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) are involved in the occurrence and progression of many human diseases. Recently, the involvement of ncRNAs in the course of EV infection has been reported. Herein, the authors focus on recent advances in the understanding of ncRNAs in EV infection from basic viral pathogenesis to clinical prospects, providing a reference basis and new ideas for disease prevention and research directions.

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“…Viral myocarditis is characterized as localized or diffuse disease of the myocardial parenchyma or interstitium caused by virus infection. After coxsackievirus B3 (CVB3) was first used to induce myocarditis in mice in 1974 by Woodruff, most of the subsequent experimental models of viral myocarditis were induced by CVB3 infection [ 1 ]. CVB3 is a nonenveloped single-stranded RNA virus belonging to the genus Enterovirus of the picornavirus family [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

TFRC upregulation promotes ferroptosis in CVB3 infection via nucleus recruitment of Sp1

et al. 2022

Cell Death Dis

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CVB3 is a single positive-strand enterovirus, and a common pathogen in myocarditis etiology. Although a number of antiviral candidates are under development, specific targeted therapy is not available for CVB3. Ferroptosis is a new type of regulatory cell death discovered in recent years. In this study, our team provided the first evidence that ferroptosis existed in CVB3 infection in vivo and in vitro by iron overload, and massive accumulation of lipid peroxides. Mechanistically, we construct a classical model of HeLa cells following a time-course infection (6, 12, 24, 36, 48 h) with CVB3 (MOI = 10). We demonstrated that the TFRC gene plays an important role in promoting ferroptosis in CVB3 infection and downregulation of TFRC attenuated the ferroptosis. Interestingly, we observed that TFRC was nuclear translocation induced by the CVB3, which was predominantly localized in the cell membrane, but redistributed to the nucleus during CVB3 infection. Moreover, we found that the transcription factor Sp1 was an essential factor that could bind to the TFRC promoter and upregulate the TFRC transcription. Collectively, these results suggest that the Sp1/TFRC/Fe axis may provide a new target for the development of therapies against CVB3 infection.

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The Role of Non-coding RNAs in Viral Myocarditis

Cited by 22 publications

References 161 publications

Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis

Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis

Essential Role of Non-Coding RNAs in Enterovirus Infection: From Basic Mechanisms to Clinical Prospects

TFRC upregulation promotes ferroptosis in CVB3 infection via nucleus recruitment of Sp1

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