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Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE185250 | GEO | 2023/10/01

REPOSITORIES: GEO

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Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis [RNA-seq]

Project description:Oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC) represents an increasing problem in the global public health. OPSCC is the most frequent malignancy in oral cavity, with an overall increasing incidence and mortality. In view of its unclear exact mechanism and lack of optimized prevention and treatment methods, new biomarkers are needed to characterize the diversity of cancer and to explore effective treatment targets. This study combined translatomics and transcriptomics to analyze the differential genes in human oral cancer and adjacent tissues, in order to provide a new perspective for the prevention and treatment of OPSCC.

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Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis [Ribo-seq]

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Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis

Project description:Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis

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Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis [RNA-seq]

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Translatomics coupled with transcriptomics reveals a novel mechanism of oral carcinogenesis [Ribo-seq]

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Translatomics combined with transcriptomics and proteomics reveals novel functional, recently evolved orphan genes in Escherichia coli O157:H7 (EHEC).

Project description:BackgroundGenomes of E. coli, including that of the human pathogen Escherichia coli O157:H7 (EHEC) EDL933, still harbor undetected protein-coding genes which, apparently, have escaped annotation due to their small size and non-essential function. To find such genes, global gene expression of EHEC EDL933 was examined, using strand-specific RNAseq (transcriptome), ribosomal footprinting (translatome) and mass spectrometry (proteome).ResultsUsing the above methods, 72 short, non-annotated protein-coding genes were detected. All of these showed signals in the ribosomal footprinting assay indicating mRNA translation. Seven were verified by mass spectrometry. Fifty-seven genes are annotated in other enterobacteriaceae, mainly as hypothetical genes; the remaining 15 genes constitute novel discoveries. In addition, protein structure and function were predicted computationally and compared between EHEC-encoded proteins and 100-times randomly shuffled proteins. Based on this comparison, 61 of the 72 novel proteins exhibit predicted structural and functional features similar to those of annotated proteins. Many of the novel genes show differential transcription when grown under eleven diverse growth conditions suggesting environmental regulation. Three genes were found to confer a phenotype in previous studies, e.g., decreased cattle colonization.ConclusionsThese findings demonstrate that ribosomal footprinting can be used to detect novel protein coding genes, contributing to the growing body of evidence that hypothetical genes are not annotation artifacts and opening an additional way to study their functionality. All 72 genes are taxonomically restricted and, therefore, appear to have evolved relatively recently de novo.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcriptomics and translatomics identify a robust inflammatory gene signature in brain endothelial cells after ischemic stroke.

Project description:Vascular endothelial function is challenged during cerebral ischemia and reperfusion. The endothelial responses are involved in inflammatory leukocyte attraction, adhesion and infiltration, blood-brain barrier leakage, and angiogenesis. This study investigated gene expression changes in brain endothelial cells after acute ischemic stroke using transcriptomics and translatomics. We isolated brain endothelial mRNA by: (i) translating ribosome affinity purification, enabling immunoprecipitation of brain endothelial ribosome-attached mRNA for translatome sequencing and (ii) isolating CD31+ endothelial cells by fluorescence-activating cell sorting for classical transcriptomic analysis. Both techniques revealed similar pathways regulated by ischemia but they showed specific differences in some transcripts derived from non-endothelial cells. We defined a gene set characterizing the endothelial response to acute stroke (24h) by selecting the differentially expressed genes common to both techniques, thus corresponding with the translatome and minimizing non-endothelial mRNA contamination. Enriched pathways were related to inflammation and immunoregulation, angiogenesis, extracellular matrix, oxidative stress, and lipid trafficking and storage. We validated, by flow cytometry and immunofluorescence, the protein expression of several genes encoding cell surface proteins. The inflammatory response was associated with the endothelial upregulation of genes related to lipid storage functions and we identified lipid droplet biogenesis in the endothelial cells after ischemia. The study reports a robust translatomic signature of brain endothelial cells after acute stroke and identifies enrichment in novel pathways involved in membrane signaling and lipid storage. Altogether these results highlight the endothelial contribution to the inflammatory response, and identify novel molecules that could be targets to improve vascular function after ischemic stroke.

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