Differential Expression of miR‐4520a Associated With Pyrin Mutations in Familial Mediterranean Fever (FMF)

Latsoudis, Helen; Mashreghi, Mir‐Farzin; Grün, Joachim R.; Chang, Hyun Dong; Stuhlmüller, Bruno; Repa, Argyro; Gergiannaki, I.; Kabouraki, E.; Vlachos, G.; Häupl, Thomas; Radbruch, Andreas; Sidiropoulos, Prodromos; Doukoumetzidis, Kimon; Kardassis, Dimitris; Niewold, Timothy B.; Boumpas, Dimitrios T.; Goulielmos, George N.

doi:10.1002/jcp.25602

Cited by 24 publications

(9 citation statements)

References 54 publications

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“…26 Moreover, in a study about the relationship between genotype and plasma miRNA expressions in patients with FMF, it has been shown that the plasma mRNA-452 expressions were increased in M694V (+) patients (more pronounced in homozygous ones) and associated with worse clinical course. 22 In another related study, Hortu et al 23 have shown that the plasma expression of 11 different miRNAs were reduced in patients with FMF compared to HCs.…”

Section: Discussionmentioning

confidence: 96%

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Assessment of Circulating Microribonucleic Acids in Patients With Familial Mediterranean Fever

2020

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Objectives: This study aims to evaluate the plasma expression of microribonucleic acids (miRNAs) that may be associated with the pathogenesis of familial Mediterranean fever (FMF). Patients and methods: Thirty patients with FMF (18 males, 12 females; mean age 9.1±4.7 years; range, 3 to 15.5 years) and 30 age-and sex-matched healthy children (18 males, 12 females; mean age 9.5±4.6 years; range, 4 to 16.5 years) were included in this study. The plasma levels of four candidate miRNAs (miRNA-16, miRNA-155, miRNA-204 and miRNA-451) were measured in all subjects. The plasma levels of miRNAs were analyzed with real-time polymerase chain reaction in attack and remission periods of patients and healthy controls (HCs). Results: Plasma miRNA-204 levels of FMF patients were decreased 6.5 fold in remission period compared to HCs (p<0.001). This decrease was more prominent in M694V mutation carriers. Plasma miRNA-155 levels of FMF patients were lower in remission period (p=0.03). Conclusion: Our findings showed significant alterations in the plasma expression of miRNA-155 and miRNA-204 in FMF patients compared to HCs. Our data suggest that miRNA-155 and miRNA-204 may be related to the pathogenesis of FMF. Further comprehensive and functional researches may help to clarify the role of miRNAs in FMF and elucidate the pathogenesis of the disease.

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Section: Discussionmentioning

confidence: 96%

“…In a study of plasma miRNA expressiongenotype association in patients with FMF, miRNA-452 expression has been shown to increase in M694V carriers. 22 Besides, Hortu et al 23 have shown that the plasma expressions of 11 different miRNAs are reduced in patients with FMF compared to healthy controls (HCs).…”

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confidence: 99%

Assessment of Circulating Microribonucleic Acids in Patients With Familial Mediterranean Fever

2020

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“…Downregulation of RAB7A further weakens lysosomal degradation by reducing the number of lysosomes and the fusion between autophagosomes and lysosomes. It has been supported that miR4659A directly regulated genes involved in autophagic response [ 40 ]. Therefore, the reduction of RAB7A indicates that the autophagy mechanism is blocked, as observed during lytic EBV replication.…”

Section: Discussionmentioning

confidence: 99%

Investigating genetic-and-epigenetic networks, and the cellular mechanisms occurring in Epstein–Barr virus-infected human B lymphocytes via big data mining and genome-wide two-sided NGS data identification

Jheng

Chen

2018

PLoS ONE

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Epstein–Barr virus (EBV), also known as human herpesvirus 4, is prevalent in all human populations. EBV mainly infects human B lymphocytes and epithelial cells, and is therefore associated with their various malignancies. To unravel the cellular mechanisms during the infection, we constructed interspecies networks to investigate the molecular cross-talk mechanisms between human B cells and EBV at the first (0–24 hours) and second (8–72 hours) stages of EBV infection. We first constructed a candidate genome-wide interspecies genetic-and-epigenetic network (the candidate GIGEN) by big database mining. We then pruned false positives in the candidate GIGEN to obtain the real GIGENs at the first and second infection stages in the lytic phase by their corresponding next-generation sequencing data through dynamic interaction models, the system identification approach, and the system order detection method. The real GIGENs are very complex and comprise protein–protein interaction networks, gene/microRNA (miRNA)/long non-coding RNA regulation networks, and host–virus cross-talk networks. To understand the molecular cross-talk mechanisms underlying EBV infection, we extracted the core GIGENs including host–virus core networks and host–virus core pathways from the real GIGENs using the principal network projection method. According to the results, we found that the activities of epigenetics-associated human proteins or genes were initially inhibited by viral proteins and miRNAs, and human immune responses were then dysregulated by epigenetic modification. We suggested that EBV exploits viral proteins and miRNAs, such as EBNA1, BPLF1, BALF3, BVRF1 and miR-BART14, to develop its defensive mechanism to defeat multiple immune attacks by the human immune system, promotes virion production, and facilitates the transportation of viral particles by activating the human genes NRP1 and CLIC5. Ultimately, we propose a therapeutic intervention comprising thymoquinone, valpromide, and zebularine to act as inhibitors of EBV-associated malignancies.

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“…Spike-binding miR-648(37), miR-19a-3p (38), miR-644a (39), and miR-320d (40), and leader-binding miR-449a(41), miR-4531 (42), and miR-204 (43) were involved in PAH, asthma, COPD and pulmonary fibrosis. Leader-binding miR-6752 is highly enriched in airway epithelial cells upon mucin overproduction (44), miR-4531 is upregulated in children with asthma, and miR-4520-3p is associated with familial Mediterranean fever (45). Hence, miRNAs targeting the leader sequence of SARS-CoV-2 might partly explain increased susceptibility of certain patients with familial or previous complications.…”

Section: Lncrnas H19 Linc05 and Fendrr Interact With Sars-cov-2 Andmentioning

confidence: 99%

MicroRNAs and long non-coding RNAs as potential candidates to target specific motifs of SARS-CoV-2

Natarelli¹,

Parca

Virgili³

et al. 2020

Preprint

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The novel Coronavirus, SARS-CoV-2 disease (COVID-19) was defined as a global pandemic and induced a severe public health crisis in 2020. Covid-19 viral infection targets the human respiratory system and, at present, no specific treatment has been identified even though certain drugs have been studied and considered apparently effective in viral progression by reducing the complications in the lung epithelium. Researchers and clinicians are still struggling to find a vaccine or a specific innovative therapeutic strategy to counter COVID-19 infection.Here we describe our study indicating that SARS-CoV-2 genome contains motif sequences in the 5´UTR leader sequence that can be selectively recognized by specific human non-coding RNAs (ncRNAs), such as micro and long non-coding RNAs (miRNAs and lncRNA). Notably, some of these ncRNAs have been already utilized as oligo-based drugs in pulmonary and virus-associated diseases. We identified three selective motifs at the 5´UTR leader sequence of SARS-CoV-2 that allow viral recognition and binding of a specific group of miRNAs, some of them characterized by “GU” seed alignments. Additionally, one seed motif within miRNAs has been found to be able to bind the 5’UTR leader sequence. Among miRNAs having thermodynamically stable binding site against leader sequence and that are able interacted with Spike transcript some are involved in pulmonary arterial hypertension and anti-viral response, i.e. miR-204, miR-3661, and miR-1343. Moreover, several miRNA candidates have been already validated in vivo and specific oligo sequence are indeed available for their inhibition or overexpression.Four lncRNAs (H19, Hotair, Fendrr, and LINC05) directly interact with spike transcript (mRNA) and viral genome.In conclusion, we suggest that specific miRNAs and lncRNAs can be potential candidates to design oligonucleotide-drugs to treat COVID-19 and that our study can provide candidate hypothesis to be eventually tested in further experimental studies.

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Differential Expression of miR‐4520a Associated With Pyrin Mutations in Familial Mediterranean Fever (FMF)

Cited by 24 publications

References 54 publications

Assessment of Circulating Microribonucleic Acids in Patients With Familial Mediterranean Fever

Assessment of Circulating Microribonucleic Acids in Patients With Familial Mediterranean Fever

Investigating genetic-and-epigenetic networks, and the cellular mechanisms occurring in Epstein–Barr virus-infected human B lymphocytes via big data mining and genome-wide two-sided NGS data identification

MicroRNAs and long non-coding RNAs as potential candidates to target specific motifs of SARS-CoV-2

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