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Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2

Numerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such...

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Autores principales: Diallo, Idrissa, Jacob, Rajesh Abraham, Vion, Elodie, Kozak, Robert A., Mossman, Karen, Provost, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9962802/
https://www.ncbi.nlm.nih.gov/pubmed/36851710
http://dx.doi.org/10.3390/v15020496
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author Diallo, Idrissa
Jacob, Rajesh Abraham
Vion, Elodie
Kozak, Robert A.
Mossman, Karen
Provost, Patrick
author_facet Diallo, Idrissa
Jacob, Rajesh Abraham
Vion, Elodie
Kozak, Robert A.
Mossman, Karen
Provost, Patrick
author_sort Diallo, Idrissa
collection PubMed
description Numerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such as microRNAs (miRNAs), which are involved in the regulation of 60% of human gene activity, remains poorly explored. Similar to research we have previously undertaken with other viruses such as Ebola and HIV, in this study we investigated the miRNA profile of lung epithelial cells following infection with SARS-CoV-2. At the 24 and 72 h post-infection time points, SARS-CoV-2 did not drastically alter the miRNome. About 90% of the miRNAs remained non-differentially expressed. The results revealed that miR-1246, miR-1290 and miR-4728-5p were the most upregulated over time. miR-196b-5p and miR-196a-5p were the most downregulated at 24 h, whereas at 72 h, miR-3924, miR-30e-5p and miR-145-3p showed the highest level of downregulation. In the top significantly enriched KEGG pathways of genes targeted by differentially expressed miRNAs we found, among others, MAPK, RAS, P13K-Akt and renin secretion signaling pathways. Using RT-qPCR, we also showed that SARS-CoV-2 may regulate several predicted host mRNA targets involved in the entry of the virus into host cells (ACE2, TMPRSS2, ADAM17, FURIN), renin–angiotensin system (RAS) (Renin, Angiotensinogen, ACE), innate immune response (IL-6, IFN1β, CXCL10, SOCS4) and fundamental cellular processes (AKT, NOTCH, WNT). Finally, we demonstrated by dual-luciferase assay a direct interaction between miR-1246 and ACE-2 mRNA. This study highlights the modulatory role of miRNAs in the pathogenesis of SARS-CoV-2.
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spelling pubmed-99628022023-02-26 Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2 Diallo, Idrissa Jacob, Rajesh Abraham Vion, Elodie Kozak, Robert A. Mossman, Karen Provost, Patrick Viruses Article Numerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such as microRNAs (miRNAs), which are involved in the regulation of 60% of human gene activity, remains poorly explored. Similar to research we have previously undertaken with other viruses such as Ebola and HIV, in this study we investigated the miRNA profile of lung epithelial cells following infection with SARS-CoV-2. At the 24 and 72 h post-infection time points, SARS-CoV-2 did not drastically alter the miRNome. About 90% of the miRNAs remained non-differentially expressed. The results revealed that miR-1246, miR-1290 and miR-4728-5p were the most upregulated over time. miR-196b-5p and miR-196a-5p were the most downregulated at 24 h, whereas at 72 h, miR-3924, miR-30e-5p and miR-145-3p showed the highest level of downregulation. In the top significantly enriched KEGG pathways of genes targeted by differentially expressed miRNAs we found, among others, MAPK, RAS, P13K-Akt and renin secretion signaling pathways. Using RT-qPCR, we also showed that SARS-CoV-2 may regulate several predicted host mRNA targets involved in the entry of the virus into host cells (ACE2, TMPRSS2, ADAM17, FURIN), renin–angiotensin system (RAS) (Renin, Angiotensinogen, ACE), innate immune response (IL-6, IFN1β, CXCL10, SOCS4) and fundamental cellular processes (AKT, NOTCH, WNT). Finally, we demonstrated by dual-luciferase assay a direct interaction between miR-1246 and ACE-2 mRNA. This study highlights the modulatory role of miRNAs in the pathogenesis of SARS-CoV-2. MDPI 2023-02-10 /pmc/articles/PMC9962802/ /pubmed/36851710 http://dx.doi.org/10.3390/v15020496 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Diallo, Idrissa
Jacob, Rajesh Abraham
Vion, Elodie
Kozak, Robert A.
Mossman, Karen
Provost, Patrick
Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2
title Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2
title_full Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2
title_fullStr Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2
title_full_unstemmed Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2
title_short Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2
title_sort altered microrna transcriptome in cultured human airway cells upon infection with sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9962802/
https://www.ncbi.nlm.nih.gov/pubmed/36851710
http://dx.doi.org/10.3390/v15020496
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