Autor: |
Dinesh Devadoss, Arpan Acharya, Marko Manevski, Dominika Houserova, Michael D. Cioffi, Kabita Pandey, Madhavan Nair, Prem Chapagain, Mehdi Mirsaeidi, Glen M. Borchert, Siddappa N. Byrareddy, Hitendra S. Chand |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
iScience, Vol 25, Iss 8, Pp 104685- (2022) |
Druh dokumentu: |
article |
ISSN: |
2589-0042 |
DOI: |
10.1016/j.isci.2022.104685 |
Popis: |
Summary: Noncoding RNAs are important regulators of mucoinflammatory response, but little is known about the contribution of airway long noncoding RNAs (lncRNAs) in COVID-19. RNA-seq analysis showed a more than 4-fold increased expression of IL-6, ICAM-1, CXCL-8, and SCGB1A1 inflammatory factors; MUC5AC and MUC5B mucins; and SPDEF, FOXA3, and FOXJ1 transcription factors in COVID-19 patient nasal samples compared with uninfected controls. A lncRNA on antisense strand to ICAM-1 or LASI was induced 2-fold in COVID-19 patients, and its expression was directly correlated with viral loads. A SARS-CoV-2-infected 3D-airway model largely recapitulated these clinical findings. RNA microscopy and molecular modeling indicated a possible interaction between viral RNA and LASI lncRNA. Notably, blocking LASI lncRNA reduced the SARS-CoV-2 replication and suppressed MUC5AC mucin levels and associated inflammation, and select LASI-dependent miRNAs (e.g., let-7b-5p and miR-200a-5p) were implicated. Thus, LASI lncRNA represents an essential facilitator of SARS-CoV-2 infection and associated airway mucoinflammatory response. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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