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Differenatiation of mRNA expression in PTX3-depleted macrophages

ABSTRACT: Differenatiation of mRNA expression in PTX3-depleted macrophages

PROVIDER: PRJNA792950 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17373819_1.fastq.gz	Fastqsanger.gz
	SRR17373819_2.fastq.gz	Fastqsanger.gz
	SRR17373820_1.fastq.gz	Fastqsanger.gz
	SRR17373820_2.fastq.gz	Fastqsanger.gz
	SRR17373821_1.fastq.gz	Fastqsanger.gz

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Differenatiation of mRNA expression in PTX3-depleted macrophages

Project description:PTX3, as the long member of the pentraxin family, is produced mainly by dendritic cells, macrophages, and endothelial cells in response to inflammation. Growing amount of studies suggest that PTX3 can exert potential contradictory roles in inflammation regulation, antimicrobial resistance, and disease pathogenesis, depending on the tissue context, cellular source, and levels of production. To characterize the potential involvement of PTX3 in macrophage function, transcriptome sequencing (RNA-seq) was performed in human THP1-derived macrophages with PTX3 depletion. Notably,genes enrichment in PI3K/AKT signaling , JAK/STAT signaling and autophagy pathway were observed in PTX3 deficiency macrophages. This study highlights the critical roles of PTX3 on regulation macrophages homeostasis.

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Differenatiation of mRNA expression in METTL3-depleted macrophages

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Project description:We aimed to investigate the effect of PTX3 on macrophages functions. After PTX3 stimulation for 18 h in THP-1 macrophages, total RNA were harvested for RNA-seq analysis of ctrl (n = 1) and PTX3 group (n = 1).

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Project description:N6-methyladenosine (m6A), the most prevalent internal messenger RNA modification, plays critical roles in diverse biological processes. To characterize the potential involvement of METTL3 in macrophage function, transcriptome sequencing (RNA-seq) was performed in human THP1-derived macrophages with METTL3 depletion. We identified 266 genes that were differentially expressed in METTL3-depleted macrophages (≥ 1.5-fold change, P < 0.05), among which 44% (118 genes) were downregulated and 56% (148 genes) were upregulated. Notably, M2 macrophages activation-associated genes were robustly enhanced in METTL3-depleted macrophages. This study highlights the critical roles of m6A on regulation macrophages homeostasis.

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Project description:The pattern recognition receptor long pentraxin-3 (PTX3) plays conflicting roles in cancer by acting as an oncosuppressor or as a pro-tumor mediator depending on tumor context. Triple negative breast cancer (TNBC) represents the most aggressive histotype of breast cancer, characterized by the lack of efficacious therapeutic targets/approaches and poor prognosis. In this study, in silico data and experimental evidences indicate that PTX3 is produced by tumor parenchyma in TNBC and that its expression levels correlate with tumor stage. On this basis, the impact of PTX3 silencing or its overexpression on the tumorigenic potential of TNBC cell lines was analyzed. Gene expression and in vitro results demonstrate that high levels of PTX3 expression confer a high aggressive/proliferative phenotype, fosters stem-like features, and rewires the energy metabolism in TNBC cells. This results in a more tumorigenic potential in vivo when TNBC cells are grafted in immune-compromised and syngeneic animals. Mechanistically, our data reveal a strong positive correlation between PTX3 expression and the antitumor activity of Toll-like receptor 4 (TLR4) inhibition in TBNC, demonstrating for the first time that PTX3-driven TNBC aggressiveness is due to PTX3-mediated activation of TLR4 signaling. Altogether, these data shed light on the role of tumor-produced PTX3 in TNBC and uncover the importance of the PTX3/TLR4 pathway for therapeutic and prognostic exploitation in TNBC.

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