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Comprehensive Characterization of the rRNA Metabolic Related Genes in Human Cancer

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Document pages: 48 pages

Abstract: Background: Although rRNA metabolic related genes have been reported to be associated with human cancer, a systematic assessment of rRNA metabolic related genes across human cancers is lacking. Thus, we perform a pan-cancer analysis of rRNA metabolic related genes across 21 human cancers.Methods: We performed a pan-cancer analysis for mRNA expression, mutation, DNA methylation, copy number variation (CNV) and clinical relevance of rRNA metabolic related genes in more than 9,000 patients across 21 human cancers from The Cancer Genome Atlas (TCGA) dataset. In addition, ten independent datasets from Gene Expression Omnibus (GEO), Cancer Cell Line Encyclopedia (CCLE) and Project Achilles datasets were used to verify our study.Findings: The landscape of rRNA metabolic related genes was established across 21 human cancers. The results suggested that rRNA metabolic related genes are upregulated in multiple cancers, particularly in digestive and respiratory system cancers. Most of the upregulated genes are associated with poor prognosis and driven by CNV rather than mutation and DNA hypomethylation. We systematically identified CNV-driven rRNA metabolic related genes with clinical relevance, including EXOSC8. Finally, functional experiments confirmed the oncogenic roles of EXOSC8 in colorectal carcinoma.Interpretation: Our study highlights the important roles of rRNA metabolic related genes in tumorigenesis as prognostic biomarkers.Funding: This work was supported by grants from the National Key R&D Program of China (2016YFC1302300) and National Nature Science Foundation of China (81772609, 81802782).Declaration of Interest: The authors have declared that no competing interests exist.Ethical Approval: Animal studies were approved by the Animal Care Committee of Wuhan University. AOM- DSS-induced CRC model and lentivirus administration were performed following the according to the methods previously described.

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