MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes

Lu, Dongchao; Chatterjee, Shambhabi; Ke, Xiaoyan; Riedel, Isabelle; Wang, Yibin; Foo, Roger; Bär, Christian; Thum, Thomas

doi:10.1016/j.yjmcc.2020.08.017

Cited by 97 publications

(106 citation statements)

References 17 publications

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“… Germany To identify miRNAs predicted to regulate ACE2 using an in-silico approach. ( Lu et al, 2020 ) 25 Zhang H July 15, 2020. US To gain insight into the expression of ACE2 in the human airway epithelia, including miRNA regulatory activity.…”

Section: Resultsmentioning

confidence: 99%

“… Downregulation in the small airway epithelium of smokers compared to non-smokers Targets the 3’UTR sequence of ACE2 mRNA miR-200c-3p ACE2 Induced overexpression resulted in downregulation of ACE2 in human cardiomyocytes. Lu et al, 2020 , Nersisyan et al, 2020b . Interaction with ACE2 was validated in HEK-293 T cells by luciferase reporter assay miR-125a-5p ACE2 Expressed in lungs, kidney and esophagus.…”

Section: Resultsmentioning

confidence: 99%

“…MiR-200c-3p interaction with ACE2 mRNA was predicted by three independent studies (#24, #26, #28) and experimentally validated in human embryonic kidney cells (HEK-293T) through luciferase reporter assays ( Lu et al, 2020 ). Also, induced overexpression of miR-200c-3p in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) resulted in lower levels of ACE2 expression (#24).…”

Section: Resultsmentioning

confidence: 99%

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The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review

Marchi¹,

Sugita²,

Centa³

et al. 2021

Infection, Genetics and Evolution

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MicroRNAs are gene expression regulators, associated with several human pathologies, including the ones caused by virus infections. Although their role in infection diseases is not completely known, they can exert double functions in the infected cell, by mediating the virus infection and/or regulating the immunity-related gene targets through complex networks of virus-host cell interactions. In this systematic review, the Pubmed, EMBASE, Scopus, Lilacs, Scielo, and EBSCO databases were searched for research articles published until October 22nd, 2020 that focused on describing the role, function, and/or association of miRNAs in SARS-CoV-2 human infection and COVID-19. Following the PRISMA 2009 protocol, 29 original research articles were selected. Most of the studies reported miRNA data based on the genome sequencing of SARS-CoV-2 isolates and computational prediction analysis. The latter predicted, by at least one independent study, 1266 host miRNAs to target the viral genome. Thirteen miRNAs were identified by four independent studies to target SARS-CoV-2 specific genes, suggested to act by interfering with their cleavage and/or translation process. The studies selected also reported on viral and host miRNAs that targeted host genes, on the expression levels of miRNAs in biological specimens of COVID-19 patients, and on the impact of viral genome mutations on miRNA function. Also, miRNAs that regulate the expression levels of the ACE2 and TMPRSS2 proteins, which are critical for the virus entrance in the host cells, were reported. In conclusion, despite the limited number of studies identified, based on the search terms and eligibility criteria applied, this systematic review provides evidence on the impact of miRNAs on SARS-CoV-2 infection and COVID-19. Although most of the reported viral/host miRNAs interactions were based on in silico prediction analysis, they demonstrate the relevance of the viral/host miRNA interaction for viral activity and host responses. In addition, the identified studies highlight the potential use of miRNAs as therapeutic targets against COVID-19, and other viral human diseases (This review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) database (#CRD42020199290).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review

Marchi¹,

Sugita²,

Centa³

et al. 2021

Infection, Genetics and Evolution

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show abstract

“…The in vitro cell culture and tissue models will also be helpful in studying SARS-CoV-2 infection, cytotoxicity, molecular mechanisms, and drug or therapy effects on cells. As multiple studies have shown, the iPSC-derived cardiomyocytes could be transfected by SARS-CoV-2 and develop cytotoxic effects and death [ 61 , 136 , 137 , 138 , 139 , 140 ]. The use of cardiac organoids will be instructive to mimic COVID-19 infection of the heart but, as of now, there is no study available.…”

Section: Limitations Of Animal Modelsmentioning

confidence: 99%

Cardiovascular Manifestations of COVID-19 Infection

Magadum

Kishore

2020

Cells

191

136

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SARS-CoV-2 induced the novel coronavirus disease (COVID-19) outbreak, the most significant medical challenge in the last century. COVID-19 is associated with notable increases in morbidity and death worldwide. Preexisting conditions, like cardiovascular disease (CVD), diabetes, hypertension, and obesity, are correlated with higher severity and a significant increase in the fatality rate of COVID-19. COVID-19 induces multiple cardiovascular complexities, such as cardiac arrest, myocarditis, acute myocardial injury, stress-induced cardiomyopathy, cardiogenic shock, arrhythmias and, subsequently, heart failure (HF). The precise mechanisms of how SARS-CoV-2 may cause myocardial complications are not clearly understood. The proposed mechanisms of myocardial injury based on current knowledge are the direct viral entry of the virus and damage to the myocardium, systemic inflammation, hypoxia, cytokine storm, interferon-mediated immune response, and plaque destabilization. The virus enters the cell through the angiotensin-converting enzyme-2 (ACE2) receptor and plays a central function in the virus’s pathogenesis. A systematic understanding of cardiovascular effects of SARS-CoV2 is needed to develop novel therapeutic tools to target the virus-induced cardiac damage as a potential strategy to minimize permanent damage to the cardiovascular system and reduce the morbidity. In this review, we discuss our current understanding of COVID-19 mediated damage to the cardiovascular system.

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“…31 miRNAs and 29 miRNAs can downregulate hypothalamic ACE2 and TMPRSS2 gene expression, respectively, suggesting that they might be useful in treating SARS-CoV-2 neuroinvasion, by blocking virus entry [36]. In another study, miR-200 c suppressed ACE2 mRNA and protein expression in rat primary cardiomyocytes and human-induced pluripotent stem cell-derived cardiomyocytes, suggesting a promising strategy to treat SARS-CoV-2 cardiovascular complications [37].…”

Section: Attachment and Entrymentioning

confidence: 98%

MicroRNAs and SARS-CoV-2 life cycle, pathogenesis, and mutations: biomarkers or therapeutic agents?

et al. 2020

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To date, proposed therapies and antiviral drugs have been failed to cure coronavirus disease 2019 (COVID-19) patients. However, at least two drug companies have applied for emergency use authorization with the United States Food and Drug Administration for their coronavirus vaccine candidates and several other vaccines are in various stages of development to determine safety and efficacy. Recently, some studies have shown the role of different human and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microRNAs (miRNAs) in the pathophysiology of COVID-19. miRNAs are non-coding single-stranded RNAs, which are involved in several physiological and pathological conditions, such as cell proliferation, differentiation, and metabolism. They act as negative regulators of protein synthesis through binding to the 3′ untranslated region (3′ UTR) of the complementary target mRNA, leading to mRNA degradation or inhibition. The databases of Google Scholar, Scopus, PubMed, and Web of Science were searched for literature regarding the importance of miRNAs in the SARS-CoV-2 life cycle, pathogenesis, and genomic mutations. Furthermore, promising miRNAs as a biomarker or antiviral agent in COVID-19 therapy are reviewed.

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MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes

Cited by 97 publications

References 17 publications

The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review

The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review

Cardiovascular Manifestations of COVID-19 Infection

MicroRNAs and SARS-CoV-2 life cycle, pathogenesis, and mutations: biomarkers or therapeutic agents?

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