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Gain-of-Function p53 Protein Transferred via Small Extracellular Vesicles Promotes Conversion of Fibroblasts to a Cancer-Associated Phenotype

ABSTRACT: Gain-of-Function p53 Protein Transferred via Small Extracellular Vesicles Promotes Conversion of Fibroblasts to a Cancer-Associated Phenotype

PROVIDER: PRJNA625457 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11548461.fastq.gz	Fastqsanger.gz
	SRR11548462.fastq.gz	Fastqsanger.gz
	SRR11548463.fastq.gz	Fastqsanger.gz
	SRR11548464.fastq.gz	Fastqsanger.gz

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Gain-of-Function p53 Protein Transferred via Small Extracellular Vesicles Promotes Conversion of Fibroblasts to a Cancer-Associated Phenotype

Project description:Crosstalk between tumor and stromal cells is essential for tumor pathogenesis. Tumor and stromal interactions consist of reciprocal signaling through cytokines, growth factors, direct cell-cell interactions, and extracellular vesicles (EVs), among others. Small EVs (≤200 nm) have been considered critical messengers of cellular communication during tumor development. Here, we demonstrated that gain-of-function (GOF) p53 protein can be packaged into small EVs and transferred to stromal cells. In this study, we performed RNA sequencing to explore the gene signature alterations in small EVs after knockdown GOF p53 expression.

2020-11-18 | GSE148698 | GEO

Gain-of-Function p53 Protein Transferred via Small Extracellular Vesicles Promotes Conversion of Fibroblasts to a Cancer-Associated Phenotype [microarray]

Project description:Gain-of-Function p53 Protein Transferred via Small Extracellular Vesicles Promotes Conversion of Fibroblasts to a Cancer-Associated Phenotype [microarray]

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Gain-of-Function p53 Protein Transferred via Small Extracellular Vesicles Promotes Conversion of Fibroblasts to a Cancer-Associated Phenotype [microarray]

Project description:We demonstrated that gain-of-function (GOF) p53 protein can be packaged into small EVs and transferred to fibroblast cells. We used microarrays to determine the gene expression of NoF 151 fibroblasts after treating with small EVs from HT29-ntsh and -shP53 cells.

2021-01-06 | GSE164248 | GEO

Gain-of-function p53 protein transferred via small extracellular vesicles promotes conversion of fibroblasts to a cancer-associated phenotype.

Project description:Tumor and stromal interactions consist of reciprocal signaling through cytokines, growth factors, direct cell-cell interactions, and extracellular vesicles (EVs). Small EVs (?200 nm) have been considered critical messengers of cellular communication during tumor development. Here, we demonstrate that gain-of-function (GOF) p53 protein can be packaged into small EVs and transferred to fibroblasts. GOF p53 protein is selectively bound by heat shock protein 90 (HSP90), a chaperone protein, and packaged into small EVs. Inhibition of HSP90 activity blocks packaging of GOF, but not wild-type, p53 in small EVs. GOF p53-containing small EVs result in their conversion to cancer-associated fibroblasts. In vivo studies reveal that GOF p53-containing small EVs can enhance tumor growth and promote fibroblast transformation into a cancer-associated phenotype. These findings provide a better understanding of the complex interactions between cancer and stromal cells and may have therapeutic implications.

| S-EPMC7957825 | biostudies-literature

Characterization of the small RNA content of Trypanosoma cruzi extracellular vesicles

Project description:A growing body of evidence in mammalian cells indicates that secreted vesicles can be used to mediate intercellular communication processes by transferring various bioactive molecules, including mRNAs and microRNAs. Based on these findings, we decided to analyze whether T. cruzi-derived extracellular vesicles contain RNA molecules and performed a deep sequencing and genome-wide analysis of a size-fractioned cDNA library (16M-bM-^@M-^S40 nt) from extracellular vesicles secreted by noninfective epimastigote and infective metacyclic trypomastigote forms. Our data show that the small RNAs contained in these extracellular vesicles originate from multiple sources, including tRNAs. In addition, our results reveal that the variety and expression of small RNAs are different between parasite stages, suggesting diverse functions. Taken together, these observations call attention to the potential regulatory functions that these RNAs might play once transferred between parasites and/or to mammalian host cells. Small RNAs profiles (16-40 nt) of epimastigote-derived extracellular vesicles, metacyclic trypomastigote-derived extracellular vesicles and metacyclic trypomastigote parental cells.

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Project description:The role of extracellular vesicles in developing artemisinin resistance in Plasmodium falciparum is not known. We have posited a role for EVs in the development of ARTr (EVs export hypothesis) (Tandoh et al.,2022).The objective of this study was to test a prediction of the EVs export hypothesis to gain insight into a putative role for EVs in the expression of the artemisinin resistant phenotype. We compared the gene expression profile of two artemisinin resistant parasites (C580R and R539T) generated by CRISPR based editing of an artemisinin susceptible parasite (Dd2) for enrichment with an EVs module of interest using gene set enrichment analysis.

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Project description:Direct conversion from fibroblast to neuron has recently been successfully induced bypassing the pluripotent state. However, the conversion takes a few months with low percentages of success. Here we found that depletion of p53, which can converted fibroblasts into three major neural lineages: neurons, astrocytes and oligodendrocytes. Furthermore, our method provided a high efficiency of conversion in aging fibroblasts, where published methods failed. This finding may help developing a prototype for neuron replacement therapy, including foraging people vulnerable to neurological disorders. p53 has been shown to inhibit reprogramming of fibroblasts to iPS cells, by depletion of p53 in human fibroblasts, we study the function of p53 in induced neuron process. By induction of p53 knockdown fibroblasts with special neuron medium, we can get mature neurons directly. In the induction process, many neurogenic transcription factors were up-regulated, and we prove that p21 is not involved in this process.

2013-04-26 | E-GEOD-46392 | biostudies-arrayexpress

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Project description:Extracellular vesicles (EVs) are nanoparticles containing various bioactive cargos, e.g., proteins, RNAs, and lipids, that are released into the environment by all cell types. They are involved in, amongst others, intercellular communication. This article presents studies on EVs produced by the probiotic yeast Saccharomyces boulardii CNCM I-745. The size distribution and concentration of EVs in the liquid culture of yeast were estimated. Moreover, the vesicles of S. boulardii were tested for their cytotoxicity against three model human intestinal cell lines. This study did not show any significant negative effect of yeast EVs on these cells under tested conditions. In addition, EVs of S. boulardii were verified for their ability to internalize in vitro with human cells and transfer their cargo. The yeast vesicles were loaded with doxorubicin, an anticancer agent, and added to the cellular cultures. Subsequently, microscopic observations revealed that these EVs transferred the chemotherapeutic to human intestinal cell lines. A cytotoxicity test confirmed the activity of the transferred doxorubicin. Detailed information about the proteins present in EVs might be important in terms of exploring yeast EVs as carriers of active molecules. Thus, proteomic analysis of the EV content was also conducted within the present study, and it allowed to identify 541 proteins after matching to the Saccharomyces Genome Database (SGD). Altogether, this study provides strong evidence that the EVs of the probiotic CNCM I-745 strain could be considered a drug delivery system.

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