Mitoribosome Defect in Hepatocellular Carcinoma Promotes an Aggressive Phenotype with Suppressed Immune Reaction

So Mee Kwon; Young-Kyoung Lee; Seongki Min; Hyun Goo Woo; Hee Jung Wang; Gyesoon Yoon

doi:10.1016/j.isci.2020.101247

Mitoribosome Defect in Hepatocellular Carcinoma Promotes an Aggressive Phenotype with Suppressed Immune Reaction

iScience. 2020 Jun 26;23(6):101247. doi: 10.1016/j.isci.2020.101247. Epub 2020 Jun 7.

Authors

So Mee Kwon¹, Young-Kyoung Lee², Seongki Min², Hyun Goo Woo³, Hee Jung Wang⁴, Gyesoon Yoon⁵

Affiliations

¹ Departments of Physiology, Ajou University School of Medicine, Suwon 16499, Korea; Departments of Biochemistry, Ajou University School of Medicine, Suwon 16499, Korea; Departments of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea. Electronic address: smkwon@ajou.ac.kr.
² Departments of Biochemistry, Ajou University School of Medicine, Suwon 16499, Korea; Departments of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea.
³ Departments of Physiology, Ajou University School of Medicine, Suwon 16499, Korea; Departments of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea.
⁴ Departments of Surgery, Ajou University School of Medicine, Suwon 16499, Korea.
⁵ Departments of Biochemistry, Ajou University School of Medicine, Suwon 16499, Korea; Departments of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea. Electronic address: ypeace@ajou.ac.kr.

Abstract

Mitochondrial 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.

Keywords: Cancer; Cancer Systems Biology; Immunology.