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Identification of microRNAs associated with aggressive choroid plexus tumor phenotypes

ABSTRACT: Identification of microRNAs associated with aggressive choroid plexus tumor phenotypes

PROVIDER: PRJNA962087 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24316000.fastq.gz	Fastqsanger.gz
	SRR24316001.fastq.gz	Fastqsanger.gz
	SRR24316002.fastq.gz	Fastqsanger.gz
	SRR24316003.fastq.gz	Fastqsanger.gz
	SRR24316004.fastq.gz	Fastqsanger.gz

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Identification of microRNAs associated with aggressive choroid plexus tumor phenotypes

Project description:We previously demonstrated that combining histological approaches with a specific DNA methylation signature for choroid plexus carcinomas (CPCs) can help to differentiate aggressive tumors from those that are not life threatening. Herein, we investigate the role of miRNAs in choroid plexus tumorigenesis, given the well-established role of miRNAs in the pathogenesis of other cancers. We characterized miRNA expression (using miRNA-seq and miRNA PCR arrays) in different CPTs in order to establish which miRNAs can serve as predictive biomarkers for CPCs compared to the less aggressive forms - choroid plexus papilloma (CPP) and atypical choroid plexus papilloma (aCPP). We performed miRNA-seq on 35 CPTs and used real-time PCR for the validation. We identified significant differences in the miRNA expression profiles between CPCs and CPPs. The specific miRNA expression signature for CPCs revealed upregulation of several miRNA members of oncogenic miRNA clusters (miR-17-92, 106a-363, 183/96/182) and downregulation of the tumor suppressive miRNA 34b/c cluster. Our findings suggest that the identified miRNAs could serve as novel biomarkers for CPCs and that targeting these deregulated miRNAs could be a promising new treatment strategy for this aggressive form of CPTs where survival rates remain below 50%.

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Gene expression data from normal mouse choroid plexus, choroid plexus papilloma and choroid plexus carcinoma

Project description:Atoh1-Cre; Myc/Myc mice developed choroid plexus papilloma and Atoh1-Cre; Myc/Myc; p53fl/fl mice developed choroid plexus carcinoma. By studying the gene expression profiles of normal choroid plexus, choroid plexus papilloma and choroid plexus carcinoma in mice, we aim to gain a better understanding of the biology of choroid plexus tumors

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Project description:Gene expression profiles generated from human tumor cells laser-microdissected from surgical samples of seven choroid plexus papillomas (Grade I WHO) as eight samples of epithelial cells lasermicrodissected from normal choroid plexus obtained at autopsy. Choroid plexus tumors are rare pediatric brain tumors derrived from the choroid plexus epithelium. Gene expression profiles of lasermicrodissected tumor cells from 7 individual choroid plexus tumor samples obtained at surgery were compared to gene expression profiles from non-neoplastic choroid plexus epithelial cells lasermicrodissected from normal non-neoplastic choroid plexus obtained at autopsy (Am J Surg Pathol. 2006 Jan;30(1):66-74.) in order to identfy genes differentially expressed in choroid plexus tumor cells.

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OTX2 homeoprotein regulates adult choroid plexus activity

Project description:Choroid plexus secretes cerebrospinal fluid important for brain development and homeostasis. The OTX2 homeoprotein is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative roles for OTX2 in choroid plexus function, including cell signaling and adhesion, and show that it regulates the expression of factors secreted into cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and also affects splicing which leads to changes in mRNA isoforms of proteins implicated in oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell autonomous target regions such as visual cortex and subventricular zone, we identified putative targets involved in cell adhesion, chromatin structure and RNA processing. Thus, OTX2 retains important roles in choroid plexus function and brain homeostasis throughout life.

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Project description:To examine the cellular and transcriptional heterogeneity of choroid plexus tumors we determined the single nucleus transcriptomes of 23,906 nuclei from normal choroid plexus and choroid plexus tumors. The resulting cellular atlas profiles cellular and transcriptional heterogeneity, copy number alterations, and cell-cell interaction networks in normal and cancerous choroid plexus. We observe changes in choroid plexus tumor epithelial cell gene transcription that correlate with genome wide methylation profiles. In addition, we characterize tumor-grade-specific tumor microenvironments that include altered macrophage and mesenchymal cell states, as well as changes in extracellular matrix components.

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