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RNA sequencing reveals the microRNA features of kidney in dengue virus-infected mouse

ABSTRACT: Background: Dengue virus (DENV) spread widely, causing not only dengue fever, dengue haemorrhagic fever, and dengue shock syndrome but also renal damage, which results in a poor prognosis. MicroRNA (miRNA) has attracted attention in recent years due to its regulatory functions in the transcriptomes of viral and host genomes. However, research on the function of miRNAs in the pathogenesis of dengue and dengue-associated nephropathy is still in the early stages. Methods: We investigated the miRNA libraries from uninfected and DENV-infected mouse kidney tissue with high-throughput miRNA-seq technology, performed genomic analysis, and subsequently, practiced target gene prediction and enrichment analysis of differentially expressed miRNAs (DEmiRNAs). Result: We identified 32 DEmiRNAs, including 19 with upregulated and 13 with downregulated expression, with miR-206-3p, miR-206, and miR-135a-5p showing significantly upregulated expression, the first two were associated with AKT phosphorylation, and the latter was associated with inflammation, however, those factors have been rarely investigated. MiR-122-5p, a potential biomarker in dengue, was downregulated in the kidney, in contrast to previous studies. Subsequently, we predicted 2209 potential target genes of the differentially expressed miRNAs and explored the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, showing the pathogenic mechanisms of dengue in which the factors participated, which included viral replication and inflammatory response. Conclusion: The current study investigates overall miRNA expression in mouse kidneys as a result of DENV-2 infection in vivo. These results may broaden the scope of knowledge about how miRNAs regulate the occurrence and development of DENV infection and in turn enhance the prevention and treatment of severe dengue and associated renal disease. In this study, RNA-Seq analysis of kidney tissues from a mouse model after DENV infection was performed to identify differential miRNA expression profiles, predicted target genes, and analyzed the biological functions and pathways involved in the regulation of differential miRNAs.

ORGANISM(S): Mus musculus

PROVIDER: GSE213108 | GEO | 2025/09/10

REPOSITORIES: GEO

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Project description:Background: Organ dysfunction, especially liver injury, caused by dengue virus (DENV) infection has been associated with fatal cases in dengue patients around the world. However, the pathophysiological mechanisms of liver involvement in dengue remain unclear. There is accumulating evidence that miRNAs are playing an important role in regulating viral pathogenesis, and it can help in diagnostic and anti-viral therapies development. Methods: We collected liver tissues of DENV-infected for small RNA sequencing to identify significantly different express miRNAs during dengue virus infection, and the identified target genes of these miRNAs were annotated by biological function and pathway enrichment. Results: 31 significantly altered miRNAs were identified, including 16 up-regulated and 15 down-regulated miRNAs. By performing a series of miRNA prediction and signaling pathway enrichment analyses, the down-regulated miRNAs of mmu-miR-484, mmu-miR-1247-5p and mmu-miR-6538 were identified to be the crucial miRNAs. Further analysis revealed that the inflammation and immune responses involving Hippo, PI3K-Akt, MAPK, Wnt, mTOR, TGF-beta, Tight junction, and Platelet activation were modulated collectively by these three key miRNAs during DENV infection. These pathways are considered to be closely associated with the pathogenic mechanism and treatment strategy of dengue patients. Conclusion: The miRNAs identified by sequencing, especially miR-484 may be the potential therapeutic targets for liver involvement in dengue patients which involves the regulation of vascular permeability and expression of inflammatory cytokines. In this study, RNA-Seq analysis of liver tissues from a mouse model after DENV infection was performed to identify differential miRNA expression profiles, predicted target genes, and analyzed the biological functions and pathways involved in the regulation of differential miRNAs, contributing to the understanding of the mechanisms of liver tissue involvement after DENV infection.

Project description:Background. Dengue caused by dengue virus (DENV) serotypes -1 to -4 is the most important mosquito-borne viral disease in the tropical and sub-tropical countries worldwide. Yet many of the pathophysiological mechanisms of host responses during DENV infection remain largely unknown and incompletely understood. Methods. Using a mouse model, the miRNA expressions in liver during DENV-1 infection was investigated using high throughput miRNA sequencing. The differential expression of miRNAs were then validated by qPCR, followed by target genes prediction. The identified miRNA targets were subjected to gene ontology (GO) annotation and pathway enrichment analysis to elucidate the potential biological pathways and molecular mechanisms associated with DENV-1 infection. Results. A total of 224 and 372 miRNAs out of 433 known mouse miRNAs were detected in the livers of DENV-1-infected and uninfected mice, respectively; of these, 207 miRNAs were present in both libraries. The miR-148a-3p and miR-122-5p were the two most abundant miRNAs in both groups. Thirty-one miRNAs were found to have at least 2-fold change in upregulation or downregulation, in which seven miRNAs were upregulated and 24 miRNAs were downregulated in the DENV-1-infected mouse livers. The miR-1a-3p was found to be the most downregulated miRNA in the DENV-1-infected mouse livers, with a significant fold change of 0.10. To validate the miRNA sequencing result, the expression pattern of 12 miRNAs, which were highly differentially expressed or most abundant, were accessed by qPCR and nine of them correlated positively with the one observed in deep sequencing. In silico functional analysis revealed that the adaptive immune responses involving TGF-beta, MAPK, PI3K-Akt, Rap1, Wnt and Ras signalling pathways were modulated collectively by 23 highly differentially expressed miRNAs during DENV-1 infection. Conclusion. This study provides the first insight into the global miRNA expressions of mouse livers in response to DENV-1 infection in vivo and the possible roles of miRNAs in modulating the adaptive immune responses during DENV-1 infection.

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RNA sequencing reveals the microRNA features of kidney in dengue virus-infected mouse

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