Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

Centa, A; Fonseca, Aline Simoneti; Ferreira, Solange; Azevedo, Marina Luise Viola de; Paula, Caroline Busatta Vaz de; Nagashima, Seigo; Machado-Souza, Cleber; Miggiolaro, Anna Flavia Ribeiro dos Santos; Baena, Cristina Pellegrino; Cavalli, Luciane R.

doi:10.1152/ajplung.00457.2020

Cited by 63 publications

(61 citation statements)

References 33 publications

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“…VEGF, a proangiogenic factor is known for its involvement in vascular leakiness and inflammation in COVID infected lung tissues [ 67 ]. Our findings confirm the recent miRNA studies in COVID patients [ 68 ] [ 69 ] [ 70 ]. The effective targetability of both host and viral genes miRNAs presents them as novel avenues to control the COVID pandemic.…”

Section: Discussionsupporting

confidence: 92%

Multilevel systems biology analysis of lung transcriptomics data identifies key miRNAs and potential miRNA target genes for SARS-CoV-2 infection

Banaganapalli

Alrayes²,

Awan

et al. 2021

Computers in Biology and Medicine

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Background The spread of a novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has affected both the public health and the global economy. The current study was aimed at analysing the genetic sequence of this highly contagious corona virus from an evolutionary perspective, comparing the genetic variation features of different geographic strains, and identifying the key miRNAs as well as their gene targets from the transcriptome data of viral infected lung tissues. Methods A multilevel robust computational analysis was undertaken for viral genetic sequence alignment, phylogram construction, genome-wide transcriptome data interpretation of virus-infected lung tissues, miRNA mapping, and functional biology networking. Results Our findings show both genetic similarities as well as notable differences in the S protein length among SARS-CoV-1, SARS-CoV-2 and MERS viruses. All SARS-CoV-2 strains showed a high genetic similarity with the parent Wuhan strain, but Saudi Arabian, South African, USA, Russia and New Zealand strains carry 3 additional genetic variations like P333L (RNA -dependant RNA polymerase), D614G (spike), and P4715L (ORF1ab). The infected lung tissues demonstrated the upregulation of 282 (56.51%) antiviral defensive response pathway genes and downregulation of 217 (43.48%) genes involved in autophagy and lung repair pathways. By miRNA mapping, 4 key miRNAs ( hsa-miR-342-5p, hsa-miR-432-5p, hsa-miR-98-5p and hsa-miR-17-5p ), targeting multiple host genes ( MYC, IL6, ICAM1 and VEGFA ) as well as SARS-CoV2 gene ( ORF1ab ) were identified. Conclusion Systems biology methods offer a new perspective in understanding the molecular reasons underlying the faster spread of SARS-CoV-2 infection. The antiviral miRNAs identified in this study may aid in the ongoing search for novel personalized therapeutic avenues for COVID patients.

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Section: Discussionsupporting

confidence: 92%

Multilevel systems biology analysis of lung transcriptomics data identifies key miRNAs and potential miRNA target genes for SARS-CoV-2 infection

Banaganapalli

Alrayes²,

Awan

et al. 2021

Computers in Biology and Medicine

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“…This can be related to the difficulty in the collection and subsequent handling of these samples. A study performed by our group, using post-mortem lung biopsies of COVID-19 patients, circumvented these limitations and was able to determine the expression of miRNAs involved in lung endothelial dysfunction ( Centa et al, 2020 ). The analysis of six post-mortem lung biopsies, revealed lower expression levels of miR-26a-5p, miR-29b-3p, and miR-34a-5p in comparison to controls ( post-mortem lung biopsies from unaffected individuals).…”

Section: Discussionmentioning

confidence: 99%

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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“…Significance of the Research: Human genetic, epigenetic, and microbiome genome variability are an intrinsic property of each Homo sapien [ 7 , 10 , 11 , 12 , 13 , 14 , 35 , 39 , 40 , 41 , 42 , 43 , 44 ]. This individual diversity in genomic expression is reflected in part by the substantial heterogeneity of miRNA species abundance, sequence variety, and complexity in human cells, tissues, and physiological systems [ 11 , 12 , 13 , 14 , 35 , 36 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

microRNA Heterogeneity, Innate-Immune Defense and the Efficacy of SARS-CoV-2 Infection—A Commentary

Lukiw

2021

ncRNA

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a member of the genus Betacoronavirus in the family Coronaviridae, possesses an unusually large single-stranded viral RNA (ssvRNA) genome of about ~29,811 nucleotides (nt) that causes severe and acute respiratory distress and a highly lethal viral pneumonia known as COVID-19. COVID-19 also presents with multiple ancillary systemic diseases and often involves cardiovascular, inflammatory, and/or neurological complications. Pathological viral genomes consisting of ssvRNA, like cellular messenger RNA (mRNA), are susceptible to attack, destruction, neutralization, and/or modulation by naturally occurring small non-coding RNAs (sncRNAs) within the host cell, some of which are known as microRNAs (miRNAs). This paper proposes that the actions of the 2650 known human miRNAs and other sncRNAs form the basis for an under-recognized and unappreciated innate-immune regulator of ssvRNA viral genome activities and have implications for the efficiency of SARS-CoV-2 invasion, infection, and replication. Recent research indicates that both miRNA and mRNA abundance, speciation, and complexity varies widely amongst human individuals, and this may: (i) In part explain the variability in the innate-immune immunological and pathophysiological response of different human individuals to the initiation and progression of SARS-CoV-2 infection in multiple tissue types; and (ii) further support our understanding of human biochemical and genetic individuality and the variable resistance of individuals to ssvRNA-mediated viral infection and disease. This commentary will briefly address current findings and concepts in this fascinating research area of non-coding RNA and innate-immunity with special reference to natural host miRNAs, SARS-CoV-2, and the current COVID-19 pandemic.

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Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients

Cited by 63 publications

References 33 publications

Multilevel systems biology analysis of lung transcriptomics data identifies key miRNAs and potential miRNA target genes for SARS-CoV-2 infection

Multilevel systems biology analysis of lung transcriptomics data identifies key miRNAs and potential miRNA target genes for SARS-CoV-2 infection

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

microRNA Heterogeneity, Innate-Immune Defense and the Efficacy of SARS-CoV-2 Infection—A Commentary

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