Pathways and microRNAs bioinformatics analyses identifying possible existing therapeutics for COVID-19 treatment

Teodori, Laura; Sestili, Piero; Madiai, Valeria; Coppari, Sofia; Fraternale, Daniele; Rocchi, Marco; Ramakrishna, Seeram; Albertini, Maria Cristina

doi:10.21203/rs.3.rs-29446/v1

Cited by 3 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The association of KD with COVID-19 provides a novel insight into the pathology of KD. Also, the associations of miRNAs and lncRNAs with pandemic COVID-19 suggested the key roles of them in COVID-19 management (Gambardella et al, 2020;Ramaiah, 2020;Teodori et al, 2020). Our study identified the significantly deregulated genes, lncRNAs, and ceRNA networks in KD.…”

Section: Discussionsupporting

confidence: 55%

Differentially expressed genes, lncRNAs, and competing endogenous RNAs in Kawasaki disease

Guo

Hua

Qian

2021

PeerJ

View full text Add to dashboard Cite

Background Kawasaki disease (KD) is an acute and febrile systemic vasculitis of unknown etiology. This study aimed to identify the competing endogenous RNA (ceRNA) networks of lncRNAs, miRNAs, and genes in KD and explore the molecular mechanisms underlying KD. Methods GSE68004 and GSE73464 datasets were downloaded from the Gene Expression Omnibus. Differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) in KD were identified using the criteria of p < 0.05 and | log2 (fold change) | ≥ 1. MicroRNAs (miRNAs) related to KD were searched from databases. The lncRNA-miRNA-mRNA networks involving the DElncRNAs and DEGs were constructed. Results A total of 769 common upregulated, 406 common downregulated DEGs, and six DElncRNAs were identified in the KD samples. The lncRNA-miRNA-mRNA network consisted of four miRNAs, three lncRNAs (including the upregulated PSORS1C3, LINC00999, and the downregulated SNHG5) and four DEGs (including the downregulated GATA3 and the upregulated SOD2, MAPK14, and PPARG). Validation in the GSE18606 dataset showed that intravenous immunoglobulin treatment significantly alleviated the deregulated profiles of the above RNAs in KD patients. Three ceRNA networks of LINC00999-hsa-miR-6780-SOD2, PSORS1C3-hsa-miR-216a-PPARG/MAPK14, and SNHG5-hsa-miR-132/hsa-miR-92-GATA3 were identified. Four genes were associated with functional categories, such as inflammatory response and vascular endothelial cell. Conclusions The ceRNA networks involve genes, such as SOD2, MAPK14, and PPARG, and lncRNAs, including PSORS1C3, LINC00999, and SNHG5, which might play a key role in the pathogenesis and development of KD by regulating inflammation.

show abstract

Section: Discussionsupporting

confidence: 55%

Differentially expressed genes, lncRNAs, and competing endogenous RNAs in Kawasaki disease

Guo

Hua

Qian

2021

PeerJ

View full text Add to dashboard Cite

show abstract

“…Despite their heterogeneity, all these compounds inhibit HDAC. The value of sharing common denominator might be three-fold: indeed it paves the way to make drug associations which 1) converge toward the same target with additive effects, 2) exert different but coherent actions by virtue of the pleiotropism of some compounds and finally, 3) allow the reduction of the doses of the single combined agents thus limiting their adverse effects ( Teodori et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…We really appreciated the investigation performed by Guan, Ni et al and would like to thank all the investigators involved who shared the clinical data which was extremely useful for COVID-19 infection disease research. This manuscript has been released as a pre-print at Research Square (Teodori et al;DOI: https://doi.org/10.21203/rs.3.rs-29446/v1).…”

Section: Data Availability Statementmentioning

confidence: 99%

MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics

et al. 2020

Self Cite

View full text Add to dashboard Cite

Over 313,000 SARS-CoV-2 positive cases have been confirmed in Italy as of 30 September 2020, and the number of deaths exceeding thirty-five thousand makes Italy among the list of most significantly affected countries in the world. Such an enormous occurrence of infections and death raises the urgent demand for effective available treatments. Discovering the cellular/molecular mechanisms of SARS-CoV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and how to plan any therapeutic approach. In this regard, we performed an in silico analysis to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. Consequently, we investigated the signalling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets, and functions. Our bioinformatics analysis predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with histone deacetylate (HDAC) pathway. Notably, our results identified ACE/ACE2-ATR1-Cholesterol-HDAC axis signals that also matched with some available clinical data. We hypothesize that the current and EMA-approved, SARS-CoV-2 off-label HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. Moreover, a ranked list of compounds is provided for further evaluation for safety, efficacy, and effectiveness.

show abstract

“…Further evaluation of top pathways targeted by miR-26b-5p occurred to be also highly linked and modulated by HDAC. This indicates a particular cross-talk between miR-26b-5p and HDAC that can be used as a therapeutic strategy 23 . Additionally, our previous publication emphasized miR-26b-5p potential role in COVID-19 associated heart failure (HF) progression 1 .…”

Section: Discussionmentioning

confidence: 99%

Alteration of circulating ACE2-network related microRNAs in patients with COVID-19

Wicik,

Eyileten,

Nowak

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Angiotensin converting enzyme 2 (ACE2) serves as the primary receptor for the SARS-CoV-2 virus and has implications for the functioning of the cardiovascular system. Based on our previously published bioinformatic analysis, in this study we aimed to analyze the diagnostic and predictive utility of miRNAs (miR-10b-5p, miR-124-3p, miR-200b-3p, miR-26b-5p, miR-302c-5p) identified as top regulators of ACE2 network with potential to affect cardiomyocytes and cardiovascular system in patients with COVID-19. The expression of miRNAs was determined through qRT-PCR in a cohort of 79 hospitalized COVID-19 patients as well as 32 healthy volunteers. Blood samples and clinical data of COVID-19 patients were collected at admission, 7-days and 21-days after admission. We also performed SHAP analysis of clinical data and miRNAs target predictions and advanced enrichment analyses. Low expression of miR-200b-3p at the seventh day of admission is indicative of predictive value in determining the length of hospital stay and/or the likelihood of mortality, as shown in ROC curve analysis with an AUC of 0.730 and a p-value of 0.002. MiR-26b-5p expression levels in COVID-19 patients were lower at the baseline, 7 and 21-days of admission compared to the healthy controls (P < 0.0001). Similarly, miR-10b-5p expression levels were lower at the baseline and 21-days post admission (P = 0.001). The opposite situation was observed in miR-124-3p and miR-302c-5p. Enrichment analysis showed influence of analyzed miRNAs on IL-2 signaling pathway and multiple cardiovascular diseases through COVID-19-related targets. Moreover, the COVID-19-related genes regulated by miR-200b-3p were linked to T cell protein tyrosine phosphatase and the HIF-1 transcriptional activity in hypoxia. Analysis focused on COVID-19 associated genes showed that all analyzed miRNAs are strongly affecting disease pathways related to CVDs which could be explained by their strong interaction with the ACE2 network.

show abstract

Pathways and microRNAs bioinformatics analyses identifying possible existing therapeutics for COVID-19 treatment

Cited by 3 publications

References 32 publications

Differentially expressed genes, lncRNAs, and competing endogenous RNAs in Kawasaki disease

Differentially expressed genes, lncRNAs, and competing endogenous RNAs in Kawasaki disease

MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics

Alteration of circulating ACE2-network related microRNAs in patients with COVID-19

Contact Info

Product

Resources

About