ArticleVirology journal2024
LINC01002 functions as a ceRNA to regulate FRMD8 by sponging miR-4324 for the development of COVID-19.
Article in Virology journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Decoding miRNA-Mediated Immunoregulation in SARS-CoV-2, HBV, HIV, and HSV Infections.Genes and immunity · 2026Review
- Pivotal Role of miRNA-lncRNA Interactions in Human Diseases.Molecular biotechnology · 2025Review
- Exploring genetic loci linked to COVID-19 severity and immune response through multi-trait GWAS analyses.Frontiers in genetics · 2025Article
- The role of long non-coding RNAs and circular RNAs in immune evasion of influenza A virus: recent advances.Frontiers in cellular and infection microbiology · 2025Review
- Long non-coding RNA MALAT1 triggers ferroptosis via interaction with FUS to enhance ACSF2 mRNA stabilization in septic acute kidney injury.The Kaohsiung journal of medical sciences · 2024Article
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16 authors.
Funding
Abstract
backgroundSyndrome coronavirus-2 (SARS-CoV-2) has developed various strategies to evade the antiviral impact of type I IFN. Non-structural proteins and auxiliary proteins have been extensively researched on their role in immune escape. Nevertheless, the detailed mechanisms of structural protein-induced immune evasion have not been well elucidated.
methodsHuman alveolar basal epithelial carcinoma cell line (A549) was stimulated with polyinosinic-polycytidylic acid (PIC) and independently transfected with four structural proteins expression plasmids, including nucleocapsid (N), spike (S), membrane (M) and envelope (E) proteins. By RT-qPCR and ELISA, the structural protein with the most pronounced inhibitory effects on IFN-β induction was screened. RNA-sequencing (RNA-Seq) and two differential analysis strategies were used to obtain differentially expressed genes associated with N protein inhibition of IFN-β induction. Based on DIANA-LncBase and StarBase databases, the interactive competitive endogenous RNA (ceRNA) network for N protein-associated genes was constructed. By combining single-cell sequencing data (GSE158055), lncRNA-miRNA-mRNA axis was further determined. Finally, RT-qPCR was utilized to illustrate the regulatory functions among components of the ceRNA axis.
resultsSARS-CoV-2 N protein inhibited IFN-β induction in human alveolar epithelial cells most significantly compared with other structural proteins. RNA-Seq data analysis revealed genes related to N protein inhibiting IFNs induction. The obtained 858 differentially expressed genes formed the reliable ceRNA network. The function of LINC01002-miR-4324-FRMD8 axis in the IFN-dominated immune evasion was further demonstrated through integrating single-cell sequencing data. Moreover, we validated that N protein could reverse the effect of PIC on LINC01002, FRMD8 and miR-4324 expression, and subsequently on IFN-β expression level. And LINC01002 could regulate the production of FRMD8 by inhibiting miR-4324.
conclusionSARS-CoV-2 N protein suppressed the induction of IFN-β by regulating LINC01002 which was as a ceRNA, sponging miR-4324 and participating in the regulation of FRMD8 mRNA. Our discovery provides new insights into early intervention therapy and drug development on SARS-CoV-2 infection.
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