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Extracellular vesicle-mediated RNA transfer contributes to inter-cellular communication in the liver tumor microenvironment

ABSTRACT: Extracellular vesicle-mediated RNA transfer contributes to inter-cellular communication in the liver tumor microenvironment

PROVIDER: PRJNA803448 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17884001.fastq.gz	Fastqsanger.gz
	SRR17884002.fastq.gz	Fastqsanger.gz
	SRR17884003.fastq.gz	Fastqsanger.gz
	SRR17884004.fastq.gz	Fastqsanger.gz
	SRR17884005.fastq.gz	Fastqsanger.gz

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Extracellular vesicle-mediated RNA transfer contributes to inter-cellular communication in the liver tumor microenvironment

Project description:Extracellular vesicles and their contents are gaining recognition as important mediators of intercellular communication through the transfer of bioactive molecules such as non-coding RNA. We evaluated the contribution of EV miRNA in intercellular communication between hepatocellular cancer cells and hepatic stellate cells. EV-based miRNA was comprehensively assessed in both cell types individually. Using co-cultures of both HCC and HSC cells in transwell and 3D spheroids culture, we established EV-based miR-126-3p as a potential EV-based miRNA mediator of HSC to HCC communication through which tumor cell migration, invasion and three-dimensional growth in spheroids could be influenced. Manipulation of miR-126-3p by enforced expression or inhibition using pre-miR-126-3p or antimiR-126-3p respectively did not alter cell viability, proliferation, or sensitivity to either sorafenib or regorafenib. In contrast, migration was decreased in HepG2 cells with enforced expression of miR-126-3p. Knockdown of miR-126-3p in HepG2 resulted in a significant increase in ADAM9 expression and in LX-2 cells increased collagen accumulation and the compactness of spheroids but did not alter the number or size of spheroids. The restoration of miR-126 in 3D-co-culture of HepG2 and LX2 cells with precursor showed significant alleviated expression of ADAM9 and VEGF, While the silencing of miR-126 was elevated the expression of ADAM9 and VEGF. These studies implicate miR-126-3p in functional effects on migration, invasion, and spheroid growth in HCC cells in the presence of HSC, and thus demonstrate the presence of functional EV RNA based intercellular signaling between HSC and HCC cells that may be relevant to tumor cell behavior.

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Directional endothelial communication by polarized extracellular vesicle release

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Directional endothelial communication by polarized extracellular vesicle release

Project description:Directional endothelial communication by polarized extracellular vesicle release

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Project description:Directional endothelial communication by polarized extracellular vesicle release

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Vesicle-mediated communication between mosquito blood cells

Project description:Single-cell RNA-Sequencing reveals vesicle-mediated communication between mosquito blood cells

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Inter-organellar communication by a mitochondrial tRNA regulates nuclear metabolic transcription

Project description:Inter-organellar communication by a mitochondrial tRNA regulates nuclear metabolic transcription

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Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

Project description:Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer to the B cell of a very restricted set of T cell EV-microRNAs (mmu-miR20a-5p, mmu-miR-25-3p and mmu-miR-155-3p). Transferred EV-microRNAs target key genes that control B cell function, including the pro-apoptotic BIM and the cell-cycle regulator PTEN. EV-microRNAs transferred in T-B cognate interactions also promote survival, proliferation and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that small EV transfer is required for the germinal center reaction and antibody production in vivo, revealing a novel mechanism that controls B cell responses through the transfer of EV-microRNAs of T cell origin. These findings provide mechanistic insight on the Griscelli syndrome, associated with a mutation in the Rab27a gene and may shed light on this pathogenesis and other immune-related and inflammatory disorders. This SuperSeries is composed of the SubSeries listed below.

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Mitochondrial-nuclear DNA interactions contribute to the regulation of nuclear transcript levels as part of the inter-organelle communication system

Project description:Nuclear and mitochondrial organelles must maintain a communication system. Loci on the mitochondrial genome were recently reported to interact with nuclear loci. To determine whether this is part of a DNA based communication system we used genome conformation capture to map the global network of DNA-DNA interactions between the mitochondrial and nuclear genomes (Mito-nDNA) in Saccharomyces cerevisiae cells grown under three different metabolic conditions. The interactions that form between mitochondrial and nuclear loci are dependent on the metabolic state of the yeast. Moreover, the frequency of specific mitochondrial - nuclear interactions (i.e. COX1-MSY1 and Q0182-RSM7) showed significant reductions in the absence of mitochondrial encoded reverse transcriptase machinery. Furthermore, these reductions correlated with increases in the transcript levels of the nuclear loci (MSY1 and RSM7). We propose that these interactions represent an inter-organelle DNA mediated communication system and that reverse transcription of mitochondrial RNA plays a role in this process. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.

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Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

Project description:Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

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Inter-organellar communication by a mitochondrial tRNA regulates nuclear metabolic transcription (RNA-Seq)

Project description:Inter-organellar communication by a mitochondrial tRNA regulates nuclear metabolic transcription (RNA-Seq)

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