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ABSTRACT: Neutral ceramidase regulates breast cancer progression

PROVIDER: PRJNA936597 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23527469_1.fastq.gz	Fastqsanger.gz
	SRR23527469_2.fastq.gz	Fastqsanger.gz
	SRR23527470_1.fastq.gz	Fastqsanger.gz
	SRR23527470_2.fastq.gz	Fastqsanger.gz
	SRR23527471_1.fastq.gz	Fastqsanger.gz

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Exosomes released from embryonic hippocampal cells under ceramide treatment carry a specific miRNA signature for sphingolipid pathway and cell differentiation

Project description:Purpose: Identification of the miRNA signature carried by the exosomes released from embryonic hippocampal cells under ceramide treatment Outcome: We investigated the role of ceramide in amplifying the differentiation signal of HN9.10 cells. Treatment of HN9.10 cells with ceramide caused the release of exosomes carrying neutral sphingomyelinase and neutral ceramidase. The analysis of exosomal miRNAs showed that 38 miRNAs were differentially expressed in a statistically significant manner, with some overexpressed miRNAs regulating genes encoding for proteins involved in biological, homeostatic, biosynthetic and small molecule metabolic processes, embryo development and cell differentiation, all phenomena that could be relevant for HN9.10 cell differentiation.

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Pseudomonas-derived Ceramidase Induces Production of Inflammatory Mediators from Human Keratinocytes via Sphingosine-1-Phosphate

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ABCA12-mediated ceramide efflux governs breast cancer stem cell function

Project description:Cancer stem cells (CSCs) drive tumor growth, metastasis, relapse, and chemoresistance. However, it’s unclear how lipid metabolism, especially sphingolipids metabolism, regulates CSCs and chemoresistance. In this study, we developed spontaneous tumor models expressing a Sox9-GFP transgenic reporter and demonstrated that cancer cells expressing high levels of SOX9 functioned as CSCs in both primary tumors and metastases. Transcriptomics analyses uncovered that SOX9high CSCs upregulate ABCA12 lipid transporter. Functionally, downregulation of ABCA12 impaired cancer stemness and chemoresistance of SOX9high cells. Through lipidomic analysis, we demonstrated that ABCA12 regulates SOX9 expression and cancer stemness by controlling ceramide abundance. Blocking ceramide hydrolysis using acid ceramidase inhibitor D-NMAPPD sensitized tumors to chemotherapy and prevented enrichment of SOX9high CSCs. These data suggest a potential strategy for targeting CSCs and overcoming chemoresistance. We further demonstrated that ceramide inhibits the YAP/TAZ signaling that is required for SOX9 expression in breast CSCs.

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Pseudomonas-derived Ceramidase Induces Production of Inflammatory Mediators from Human Keratinocytes via Sphingosine-1-Phosphate

Project description:A Pseudomonas aeruginosa-derived neutral ceramidase (PaCDase) isolated from a patient with atopic dermatitis was shown to effectively degrade ceramide in the presence of Staphylococcus aureus-derived lipids or neutral detergents. To understand the effect of ceramide metabolites on the functions of differentiating keratinocytes, we have conducted genes expressions analysis from PaCDase-, sphingosine-1-phosphate (S1P)-treated or untreated three-dimensionally cultured human primary keratinocytes, which form a stratum corneum, in the presence of Triton X-100 using high resolution DNA microarray. To evaluate the effects of PaCDase and S1P on keratinocyte functions, we applied an epicutaneous 24-h patch test on the EPI-Model in keratinocyte serum-free medium (keratinocyte-SFM) (Invitrogen; Carlsbad, CA, USA) by the method of Spiekstra et al. [25] with some modification. The Triton X-100 treated samples were labeled using Cy5, and the PaCDase or S1P samples were labeled with Cy3.

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