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A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

ABSTRACT: We first treated LX-2 cells with vehicle or HHT (1μM and 5μM) for 6 hours. Then, RNA sequencing was conducted to quantify the mRNA expression level of vehicle-treated or HHT-treated LX-2 cells. HHT-induced expression changes were obtained based on the resultant data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180243 | GEO | 2021/07/18

REPOSITORIES: GEO

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Project description:Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and arteriovenous malformations in visceral organs. HHT is predominantly caused by mutations in ENG and ACVRL1, Which both belong to the TGF-M-NM-2 signalling pathway. Further knowledge on how a disturbance of the TGF-M-NM-2 signalling pathway leads to HHT manifestations is needed in order to identify potential therapeutic targets. As long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and constitute a sizable fraction of the human transcriptome, we wanted to assess whether lncRNAs play a role in the molecular pathogenesis of HHT. Here we used microarray analysis to profile lncRNAs to compare the expression of HHT telangiectasial and HHT non-telangiectasial nasal tissue from the same patient in a paired design. The microarray probes were re-annotated using the GENCODE v.16 dataset, identifying 4,810 probes mapping to 2,811 lncRNAs. By comparing HHT telangiectasial tissue versus HHT non-telangiectasial tissue, we identified 42 lncRNAs that are differentially expressed (q<0.001). Using GREAT, a tool that assumes cis-regulation, we showed that differently expressed lncRNAs are enriched for genomic loci involved in key pathways concerning HHT. Our study identified lncRNAs that are aberrantly expressed in HHT telangiectasia and indicates that lncRNAs may contribute to regulate protein-coding loci in HHT. Which suggest that the lncRNA component of the transcriptome deserves more attention in HHT. A deeper understanding of lncRNAs and their role in telangiectasia formation possesses potential for discovering therapeutic targets in HHT. Gene expression profiling of 80 paired nasal samples from patients with hereditary Haemorrhagic Telangiectasia (HHT), representing telangiectasial and non-telangiectasial (normal) tissue respectively. The patients were divided into HHT1 or HHT2 in regard to the germline mutation in ENG (HHT1) or ACVRL1 (HHT2). Additional controls were healthy siblings (not carrying the germline mutation) and external controls. The study was conducted using Agilent-028004 SurePrint G3 Human GE 8x60K Microarray platform.

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A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

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