Author Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers

Yuan, Yuan; Ju, Young Seok; Kim, Young-wook; Li, Jun; Wang, Yumeng; Yoon, Christopher J.; Yang, Yang; Creighton, Chad J.; Weinstein, John N.; Xu, Yanxun; Han, Leng; Kim, Hyung-Lae; Nakagawa, Hidewaki; Park, Keunchil; Campbell, Peter J.; Liang, Han

doi:10.1038/s41588-020-0629-y

Cited by 20 publications

(52 citation statements)

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“…1A). This pattern closely resembled the spectra seen in mammals (Mikhailova et al 2022) and human cancers (Yuan et al 2020; Ju et al 2014). Next, we collected data on the mean annual water temperatures for each fish species (Methods) and analyzed its relationship with the 12 types of substitutions in the mtDNA mutational spectrum.…”

Section: Resultssupporting

confidence: 81%

“…Polymerase-induced mutations are expected to be symmetrical and enriched in A H >G H and T H >C H (Lee and Johnson 2006). However, the asymmetrical nature of mtDNA mutations observed in our study and other research (Arbeithuber et al 2020; Mikhailova et al 2022), (Yuan et al 2020; Ju et al 2014) and the positive relationship between A H >G H and temperature and longevity requires an alternative explanation, potentially involving an additional mutagen that affects predominantly the single-stranded heavy chain during mtDNA replication (Fig S1.1). The temperature sensitivity of the mutational spectrum (Fig 1 - 4) may be due to increased oxidative damage in warm, highly-metabolic species (Martin and Palumbi 1993).…”

Section: Discussionsupporting

confidence: 53%

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A>G substitutions on a heavy chain of mitochondrial genome marks an increased level of aerobic metabolism in warm versus cold vertebrates

Mikhailova

Shamanskiy

Mihailova

et al. 2020

Preprint

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Mitochondrial mutational signature is very conserved and low deviations between species have been associated with longevity. By reconstructing species-specific mtDNA mutational spectrum for ray-finned fishes (Actinopterygii), we observed that temperature is a strong additional factor shaping the mtDNA mutational spectrum in ectotherms. The analysis of mammalian endotherms, with a special focus on species with temporarily or permanently low metabolic rates (hibernators, daily torpors, naked mole rat, etc.), confirmed the temperature effect, suggesting that two main factors shape between-species variation in mitochondrial mutational spectra: longevity and temperature.

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Section: Resultssupporting

confidence: 81%

Section: Discussionsupporting

confidence: 53%

A>G substitutions on a heavy chain of mitochondrial genome marks an increased level of aerobic metabolism in warm versus cold vertebrates

Mikhailova

Shamanskiy

Mihailova

et al. 2020

Preprint

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“…We also noticed a global increase of mitochondrial RNA content in shVRK3 versus shCTRL cells (FigS5A). Consequently, we wondered if the overexpression of OXPHOS-related genes resulted from transcriptional modulations only or could also reflect a variation in term of mitochondrial DNA (mtDNA) content as large variations in mitochondria copy number were reported in some tumors 27 .…”

Section: Gene Overexpression After Vrk3 Kd Mainly Restricted To Metab...mentioning

confidence: 99%

VRK3 depletion induces cell cycle arrest and metabolic reprogramming of Pontine Diffuse Midline Glioma (DMG)-K27 altered cells

Menez

Kergrohen

Sasha

et al. 2023

Preprint

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We previously identified VRK3 as a specific vulnerability in DMG-H3K27M cells in a synthetic lethality screen targeting the whole kinome. The aim of the present study was to elucidate the mechanisms by which VRK3 depletion impact DMG-K27M cell fitness. Gene expression studies after VRK3 knockdown emphasized the inhibition of genes involved in G1/S transition of the cell cycle resulting in growth arrest in G1. Additionally, a massive modulation of genes involved in chromosome segregation was observed, concomitantly with a reduction in the level of phosphorylation of serine 10 and serine 28 of histone H3 supporting the regulation of chromatin condensation during cell division. This last effect could be partly due to a concomitant decrease of the chromatin kinase VRK1 in DMG following VRK3 knock-down. Furthermore, a metabolic switch specific to VRK3 function was observed towards increased oxidative phosphorylation without change in mitochondria content, that we hypothesized would represent a cell rescue mechanism. This study further explored the vulnerability of DMG-H3K27M cells to VRK3 depletion suggesting potential therapeutic combinations, e.g. with the mitochondrial ClpP protease activator ONC201.

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“…The central role of mitochondria in this process is critical. Pan-cancer mitochondrial-gene analysis displayed that mitochondrion genomic alterations and nuclear mitochondrial were closely associated with 38 tumor types [6]. Some researches had showed the roles of mitochondrial genes and its relationship with the survival status of cancer patients.…”

Section: Introductionmentioning

confidence: 99%

“…Mitochondria play an indispensably pivotal role in this process. Mitochondrial gene analysis of pan-cancer revealed that nuclear mitochondrial genomic alterations were closely associated among 38 tumor types [6]. There are many studies to explore the functions of mitochondrial-related genes in cancer and how they are connected to prognosis.…”

Section: Introductionmentioning

confidence: 99%

A novel signature model based on mitochondrial-related genes for predicting survival of colon adenocarcinoma

Gao

Xing

2022

BMC Med Inform Decis Mak

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Background Colon cancer is the foremost reason of cancer-related mortality worldwide. Colon adenocarcinoma constitutes 90% of colon cancer, and most patients with colon adenocarcinoma (COAD) are identified until advanced stage. With the emergence of an increasing number of novel pathogenic mechanisms and treatments, the role of mitochondria in the development of cancer, has been studied and reported with increasing frequency. Methods We systematically analyzed the effect of mitochondria-related genes in COAD utilizing RNA sequencing dataset from The Cancer Genome Atlas database and 1613 mitochondrial function-related genes from MitoMiner database. Our approach consisted of differentially expressed gene, gene set enrichment analysis, gene ontology terminology, Kyoto Encyclopedia of Genes and Genomes, independent prognostic analysis, univariate and multivariate analysis, Kaplan–Meier survival analysis, immune microenvironment correlation analysis, and Cox regression analysis. Results Consequently, 8 genes were identified to construct 8 mitochondrial-related gene model by applying Cox regression analysis, CDC25C, KCNJ11, NOL3, P4HA1, QSOX2, Trap1, DNAJC28, and ATCAY. Meanwhile, we assessed the connection between this model and clinical parameters or immune microenvironment. Risk score was an independent predictor for COAD patients’ survival with an AUC of 0.687, 0.752 and 0.762 at 1-, 3- and 5-year in nomogram, respectively. The group with the highest risk score had the lowest survival rate and the worst clinical stages. Additionally, its predictive capacity was validated in GSE39582 cohort. Conclusion In summary, we established a prognostic pattern of mitochondrial-related genes, which can predict overall survival in COAD, which may enable a more optimized approach for the clinical treatment and scientific study of COAD. This gene signature model has the potential to improve prognosis and treatment for COAD patients in the future, and to be widely implemented in clinical settings. The utilization of this mitochondrial-related gene signature model may be benefit in the treatments and medical decision-making of COAD.

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Author Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers

Cited by 20 publications

References 0 publications

A>G substitutions on a heavy chain of mitochondrial genome marks an increased level of aerobic metabolism in warm versus cold vertebrates

A>G substitutions on a heavy chain of mitochondrial genome marks an increased level of aerobic metabolism in warm versus cold vertebrates

VRK3 depletion induces cell cycle arrest and metabolic reprogramming of Pontine Diffuse Midline Glioma (DMG)-K27 altered cells

A novel signature model based on mitochondrial-related genes for predicting survival of colon adenocarcinoma

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