The Diverse Roles of microRNAs at the Host–Virus Interface

Bernier, Annie; Sagan, Selena M.

doi:10.3390/v10080440

Cited by 95 publications

(112 citation statements)

References 232 publications

(255 reference statements)

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“…The sponging effect of circRNAs has been shown to be more efficient than that of the linear miRNA and lncRNA transcripts [29,48]. It has previously been shown that various DNA and RNA viruses (herpesviruses, polyomaviruses, retroviruses, and hepaciviruses) could modulate viral replication via miRNA- mediated gene regulation [49,50]. In contrast, the role of circRNA in viral replication is less well understood.…”

Section: Discussionmentioning

confidence: 99%

Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation

Zhang

Chu

Wen

et al. 2020

Emerging Microbes & Infections

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Circular RNAs (circRNAs) are an integral component of the host competitive endogenous RNA (ceRNA) network. These noncoding RNAs are characterized by their unique splicing reactions to form covalently closed loop structures and play important RNA regulatory roles in cells. Recent studies showed that circRNA expressions were perturbed in viral infections and circRNAs might serve as potential antiviral targets. We investigated the host ceRNA network changes and biological relevance of circRNAs in human lung adenocarcinoma epithelial (Calu-3) cells infected with the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). A total of ≥49337 putative circRNAs were predicted. Among the 7845 genes which generated putative circRNAs, 147 (1.9%) of them each generated ≥30 putative circRNAs and were involved in various biological, cellular, and metabolic processes, including viral infections. Differential expression (DE) analysis showed that the proportion of DE circRNAs significantly (P < 0.001) increased at 24 h-post infection. These DE circRNAs were clustered into 4 groups according to their time-course expression patterns and demonstrated inter-cluster and intracluster variations in the predicted functions of their host genes. Our comprehensive circRNA-miRNA-mRNA network identified 7 key DE circRNAs involved in various biological processes upon MERS-CoV infection. Specific siRNA knockdown of two selected DE circRNAs (circFNDC3B and circCNOT1) significantly reduced MERS-CoV load and their target mRNA expression which modulates various biological pathways, including the mitogen-activated protein kinase (MAPK) and ubiquitination pathways. These results provided novel insights into the ceRNA network perturbations, biological relevance of circRNAs, and potential host-targeting antiviral strategies for MERS-CoV infection.

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Section: Discussionmentioning

confidence: 99%

Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation

Zhang

Chu

Wen

et al. 2020

Emerging Microbes & Infections

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“…LMP2A increased survivin by activating the nuclear factor-κB (NF-κB) pathway for resistance from serum deprivation-induced apoptosis in GC cells [13]. At least 44 mature BART miRNAs have been identified [14]. BART miRNAs are expressed at high levels in all EBV-associated carcinomas such as NPC and GC.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2

2020

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Although Epstein-Barr virus (EBV) is known to encode over 40 different miRNAs of its own, the roles of most EBV miRNAs remain unknown. Disabled homolog 2 (DAB2) is a putative tumor suppressor, but its role in gastric carcinoma (GC), especially in EBV-associated GC, needs to be clarified. Our qRT-PCR and mRNA microarray results showed that DAB2 expression was down-regulated in EBV-positive GC cells compared to EBV-negative cells. Four BART miRNAs that might target DAB2 were predicted, and we found, using a luciferase reporter assay, that miR-BART1-3p directly targeted the 3'-UTR of DAB2. The miR-BART1-3p transfection decreased DAB2 expression at both mRNA and protein levels, while transfection of an inhibitor of miR-BART1-3p, miR-BART1-3p(i), increased DAB2 expression. In addition, miR-BART1-3p as well as siDAB2 increased migration and decreased apoptosis. Meanwhile, miR-BART1-3p(i) or pcDNA3.1-DAB2 transfection decreased migration and increased apoptosis in EBV-infected GC cells. Furthermore, decreased migration by miR-BART1-3p(i) was abrogated by co-transfected siDAB2, while decreased migration by miR-BART1-3p(i) was further suppressed by a co-transfected DAB2 over-expression vector. Our data suggest that miR-BART1-3p plays an important role in the tumorigenesis of EBV-associated GC by directly targeting DAB2.

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“…MicroRNAs are known to regulate diverse biological pathways including various steps in viral replication [6]. Hence, we studied the role of host miRNAs in regulating viral replication by predicting the host miRNA binding sites among the genome of these viruses.…”

Section: Introductionmentioning

confidence: 99%

In-silicoanalysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

Periwal

Sarma

Arora

et al. 2020

Preprint

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Recently a novel coronavirus (SARS-CoV-2) emerged from Wuhan, China and has infected more than 571000 people leading to more than 26000 deaths. Since SARS-CoV-2 genome sequences show similarity with those of SARS, we sought to analyze all the available SARS-CoV-2 genomes based on the insights obtained from SARS genome specifically focusing on non-coding RNAs.Here, results are presented from the dual approach i.e identifying host encoded miRNAs that might regulate viral pathogenesis as well as identifying viral encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing first approach resulted in the identification of 10 host encoded miRNAs that could target the genome of both the viruses (SARS-CoV-2 and SARS reference genome). Interestingly our analysis revealed that there is significantly higher number of host miRNAs that could target SARS-CoV-2 genome as compared to the SARS reference genome. Results from second approach involving SARS-CoV-2 and SARS reference genome identified a set of virus encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar "GA" rich motif in SARS-CoV-2 genome that was shown to play a vital role in lung pathogenesis during severe SARS infections. Hence, we successfully identified human and virus encoded miRNAs that might regulate pathogenesis of both these coronaviruses and the fact that more number of host miRNAs could target SARS-CoV-2 genomes possibly reveal as to why this virus follows mild pathogenesis in healthy individuals. We identified non-coding sequences in SARS-CoV-2 genomes that were earlier reported to contribute towards SARS pathology. The study provides insights into the overlapping sequences among these viruses for their effective inhibition as well as identifying new drug targets that could be used for development of new antivirals.

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The Diverse Roles of microRNAs at the Host–Virus Interface

Cited by 95 publications

References 232 publications

Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation

Competing endogenous RNA network profiling reveals novel host dependency factors required for MERS-CoV propagation

Epstein-Barr virus miR-BART1-3p suppresses apoptosis and promotes migration of gastric carcinoma cells by targeting DAB2

In-silicoanalysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

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