文章基本信息

标题：Mitoribosome Defect in Hepatocellular Carcinoma Promotes an Aggressive Phenotype with Suppressed Immune Reaction
本地全文：下载
作者：So Mee Kwon ; Young-Kyoung Lee ; Seongki Min 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：6
页码：1-41
DOI：10.1016/j.isci.2020.101247
语种：English
出版社：Elsevier
摘要：SummaryMitochondrial ribosomes (mitoribosomes), the specialized translational machinery for mitochondrial genes, exclusively encode the subunits of the oxidative phosphorylation (OXPHOS) system. Although OXPHOS dysfunctions are associated with hepatic disorders including hepatocellular carcinoma (HCC), their underlying mechanisms remain poorly elucidated. In this study, we aimed to investigate the effects of mitoribosome defects on OXPHOS and HCC progression. By generating a gene signature from HCC transcriptome data, we developed a scoring system, i.e., mitoribosome defect score (MDS), which represents the degree of mitoribosomal defects in cancers. The MDS showed close associations with the clinical outcomes of patients with HCC and with gene functions such as oxidative phosphorylation, cell-cycle activation, and epithelial-mesenchymal transition. By analyzing immune profiles, we observed that mitoribosomal defects are also associated with immunosuppression and evasion. Taken together, our results provide new insights into the roles of mitoribosome defects in HCC progression.Graphical AbstractDisplay OmittedHighlights•A set of down-regulated MRPs in HCC cause mitoribosomal defects•Mitoribosomal defects are linked to aggressive molecular features and poor prognosis•Mitoribosomal defects in HCC are associated with immunosuppression and evasion•TGF-β signaling pathway is a crucial mechanism to mediate mitoribosomal defects in HCCImmunology; Cancer Systems Biology; Cancer