Project description:Extracellular vesicles, including exosomes, and exomere nanoparticles, are under intense investigation for cargo that may serve as clinical biomarkers or therapeutic targets. Here, we report discovery of a new extracellular nanoparticle, termed supermeres. We performed LC/MS-MS proteomics analyses on gradient-purified sEVs, NVs, exomeres and supermeres. The proteomic profile of supermeres is clearly distinct from that of sEVs, NVs and exomeres. This study identifies a new functional nanoparticle replete with potential circulating biomarkers and therapeutic targets that can be exploited for clinical benefit in a host of diseases.
Project description:RNA-Seq of cellular and extracellular samples from DiFi cells. The distribution of extracellular RNA among cells, sEV pellet, exomeres and supermeres is distinct.
Project description:Glioblastoma is a grade IV glioma of heterogeneous nature which complicates disease pathophysiology and biomarker research. Thus, the aim of our meta-analysis is to identify long noncoding RNAs (lncRNAs) and protein coding genes (PCGs) that are differentially expressed over different glioblastoma tissue datasets. Small RNA-seq of glioblastoma tissues was also performed to identify differentially expressed microRNAs (miRNAs) relative to paired controls.
Project description:Extracellular vesicles, including exosomes, and exomere nanoparticles, are under intense investigation for cargo that may serve as clinical biomarkers or therapeutic targets. Here, we report discovery of a new extracellular nanoparticle, termed supermeres. We performed LC/MS-MS proteomics analyses on gradient-purified sEVs, NVs, exomeres and supermeres. The proteomic profile of supermeres is clearly distinct from that of sEVs, NVs and exomeres This study identifies a new functional nanoparticle replete with potential circulating biomarkers and therapeutic targets that can be exploited for clinical benefit in a host of diseases.
Project description:Glioblastoma, the most aggressive form of brain cancer, remains a significant global contributor to mortality. Predictions of its increasing incidence in the coming decades underscore the need for more effective treatment strategies. Caerin 1.1 and 1.9, host defence peptides originally isolated from the skin secretions of an Australian tree frog, have exhibited tumour growth inhibition against a diverse spectrum of tumours in vitro. In this study, we reaffirm their potential by demonstrating their inhibitory impact on glioblastoma growth through CCK8 assays. Furthermore, caerin 1.1 and 1.9 effectively curtailed the migration of all tested glioblastoma cells in a cell scratch assay.Quantitative proteomic analysis was employed to investigate the molecular mechanism underlying the anti-proliferative activity.
Project description:Long non-coding RNAs (lncRNAs) are increasingly recognized as important players in transcription and epigenetic-driven cell diversification. So far, lncRNA function in more dynamic transcriptional reprogramming, i.e drug response, has been largely unexplored. Here, we investigated the regulatory circuits induced by chemotherapy in glioblastoma, the most aggressive and clinically refractory brain cancer. We performed a detailed characterization of the cellular and transcriptional response of glioblastoma stem-like cells to the alkylating agent temozolomide (TMZ). We found that in addition to mRNAs, TMZ affects the expression of a large number of non-coding RNAs (miRNAs, snoRNAs, lncRNAs). Our global transcriptome analysis provides a comprehensive characterization of regulatory circuits involving transcription factors, mRNAs, miRNAs and lncRNAs. To analyse the putative functions of these largely unknown RNA molecules, we developed a pipeline to integrate small and large RNA-seq data from multiple public databases and our own experiments. This led to the identification of the RNA interactome of glioblastoma and allowed us to define regulatory loops mediated by lncRNAs. We identified 22 key lncRNAs involved in transcriptional regulatory motifs, and three lncRNAs associated with patient prognosis, independent of other known response predictors. The investigation of TMZ-induced molecular networks in glioblastoma highlights novel coding and non-coding RNA-based predictors of glioblastoma chemoresistance, as well as potential targets to counteract such resistance.
Project description:Long non-coding RNAs (lncRNAs) are increasingly recognized as important players in transcription and epigenetic-driven cell diversification. So far, lncRNA function in more dynamic transcriptional reprogramming, i.e drug response, has been largely unexplored. Here, we investigated the regulatory circuits induced by chemotherapy in glioblastoma, the most aggressive and clinically refractory brain cancer. We performed a detailed characterization of the cellular and transcriptional response of glioblastoma stem-like cells to the alkylating agent temozolomide (TMZ). We found that in addition to mRNAs, TMZ affects the expression of a large number of non-coding RNAs (miRNAs, snoRNAs, lncRNAs). Our global transcriptome analysis provides a comprehensive characterization of regulatory circuits involving transcription factors, mRNAs, miRNAs and lncRNAs. To analyse the putative functions of these largely unknown RNA molecules, we developed a pipeline to integrate small and large RNA-seq data from multiple public databases and our own experiments. This led to the identification of the RNA interactome of glioblastoma and allowed us to define regulatory loops mediated by lncRNAs. We identified 22 key lncRNAs involved in transcriptional regulatory motifs, and three lncRNAs associated with patient prognosis, independent of other known response predictors. The investigation of TMZ-induced molecular networks in glioblastoma highlights novel coding and non-coding RNA-based predictors of glioblastoma chemoresistance, as well as potential targets to counteract such resistance.