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Human microRNA-122b-5p regulates chikungunya virus replication in macrophages by directly targeting viral 3'-UTR and cellular histone deacetylase 4

ABSTRACT: Human microRNA-122b-5p regulates chikungunya virus replication in macrophages by directly targeting viral 3'-UTR and cellular histone deacetylase 4

PROVIDER: PRJNA774551 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16574269_1.fastq.gz	Fastqsanger.gz
	SRR16574269_2.fastq.gz	Fastqsanger.gz
	SRR16574270_1.fastq.gz	Fastqsanger.gz
	SRR16574270_2.fastq.gz	Fastqsanger.gz
	SRR16574271_1.fastq.gz	Fastqsanger.gz

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Project description:Meis1 is a transcription factor involved in a broad range of functions including development and proliferation and has been previously shown to harness cell cycle progression. This study aimed to investigate the regulation of Meis1 by long non-coding RNAs (lncRNAs) and their sponged microRNAs (miRNAs) and hence the impact of this regulatory axis on cell proliferation. Using in-silico analysis, miR-499-5p was predicted to target Meis1 and Malat1 was predicted and previously proven to sponge miR-499-5p. We showed that forcing the expression of miR-499-5p downregulates Meis1 expression in C166 cell line by directly binding to its 3’UTR. In addition, Malat1 knockdown significantly increases miR-499-5p expression, subsequently suppressing Meis1 mRNA and protein expression levels. Furthermore, the impact of manipulating the Malat1/miR-499-5p/Meis1 axis on cellular proliferation was assessed using the BrdU incorporation assay. We demonstrated that upon knockdown of Malat1, mimicking with miR-499-5p, or knockdown of Meis1, cell proliferation was induced. Gene Ontology, KEGG and Reactome enrichment analyses were performed on proteins detected by mass spectrometry following manipulation of the Malat1/miR-499-5p/Meis1 axis. The data revealed a multitude of differentially expressed proteins (DEPs) significantly enriched in processes related to cell cycle, cell division and proliferation. These DEPs were also involved in key signaling pathways, such as Wnt and mTOR, known to play critical roles in cell proliferation and cell cycle. Finally, since Malat1 and miR-499-5p are conserved in humans and mice, we examined the expression pattern of both non-coding RNAs (ncRNAs) in the hearts of neonatal, postnatal, and adult mice, representing models of proliferative and non-proliferative tissues. We demonstrated a paradoxical expression pattern, where Malat1 is underexpressed while miR-499-5p is overexpressed in proliferative neonatal cardiomyocytes. Collectively, our findings confirm that Malat1 sponges miR-499-5p which directly regulates Meis1, and that Malat1/miR-499-5p/Meis1 axis has a pivotal influence on cellular proliferation.

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Human microRNA-122b-5p regulates chikungunya virus replication in macrophages by directly targeting viral 3'-UTR and cellular histone deacetylase 4

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