In colonic ρ0 (rho0) cells reduced mitochondrial function mediates transcriptomic alterations associated with cancer

Penrose, Harrison M.; Heller, Sandra; Cable, Chloe; Nakhoul, Hani; Ungerleider, Nate; Baddoo, Melody; Pursell, Zachary F.; Flemington, Erik K.; Crawford, Susan E.; Savkovic, Suzana D.

doi:10.18632/oncoscience.386

Cited by 10 publications

(10 citation statements)

References 48 publications

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“…119 Studies using p0 cells, which are deficient in mitochondrial energy function, suggest that multiple established regulators of CRC depend on reduced mitochondrial function for their expression and are linked to lower patient survival. 120 CRC cells exhibit remodeling of intracellular calcium homeostasis characterized by increased mitochondrial calcium storage. 121 This increased mitochondrial calcium storage was dependent on aerobic glycolysis metabolism and contributed to enhanced cell proliferation, invasion, and resistance to cell death.…”

Section: Gut Microbiome Signaling To Mitochondria -Ibdmentioning

confidence: 99%

Gut bacteria signaling to mitochondria in intestinal inflammation and cancer

2019

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The gastrointestinal microbiome plays a pivotal role in physiological homeostasis of the intestine as well as in the pathophysiology of diseases including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Emerging evidence suggests that gut microbiota signal to the mitochondria of mucosal cells, including epithelial cells and immune cells. Gut microbiota signaling to mitochondria has been shown to alter mitochondrial metabolism, activate immune cells, induce inflammasome signaling, and alter epithelial barrier function. Both dysbiosis of the gut microbiota and mitochondrial dysfunction are associated with chronic intestinal inflammation and CRC. This review discusses mitochondrial metabolism of gut mucosal cells, mitochondrial dysfunction, and known gut microbiota-mediated mitochondrial alterations during IBD and CRC.

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Section: Gut Microbiome Signaling To Mitochondria -Ibdmentioning

confidence: 99%

Gut bacteria signaling to mitochondria in intestinal inflammation and cancer

2019

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“…In the present study, the mitochondrial mass of C6ρ0 cells was notably decreased compared with the mitochondrial mass in C6 cells. The hypothesis was that the decrease of mtDNA content in C6ρ0 cells led to mitochondrial dysfunction and that changes in energy metabolism and ATP content may destroy unconstrained tumor cell proliferation and invasion ( 35 ). A series of cellular changes and diseases are closely associated with mtDNA mutations ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of mtDNA depletion from C6 glioma cells and characteristics of the generated C6ρ0 cells

Jin

Luan

et al. 2021

Mol Med Rep

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Malignant tumors of the central nervous system (CNS) are among the types of cancer with the poorest prognosis and glioma is the commonest primary CNS tumor. A mitochondrial DNA (mtDNA)-depleted cell line C6ρ0 was generated from C6 glioma cells after long-term exposure to ethidium bromide and 2' ,3'-dideoxycytidine in order to determine the effect of mtDNA damage on cell proliferation and pathological changes in glioma cells. Single cell clones were isolated and identified after 42 days of incubation. Repopulated cybrids were formed when the clonal C6ρ0 cells were fused with rat platelets and no difference was observed in their growth in a selective medium without uridine and pyruvate compared with the growth of the parent C6 cells. Disruption of mtDNA resulted in changes in mitochondrial morphology, decreased cell proliferation, reduced intracellular reactive oxygen species and intracellular ATP, along with decreased mtDNA and mitochondrial membrane potential in C6ρ0 cells compared with the C6 cells. Taken together, C6ρ0 cells without mtDNA were established for the first time and their characteristics were compared with parent cells. This C6ρ0 cell line could be used to explore the contribution of mitochondrial dysfunction and mtDNA mutations in the pathogenesis of glioma.

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“…High HSF4 expression was an independent prognostic factor of poor OS for colorectal cancer (46). Decreased levels of calmodulin-like 6 (CALML6) has been linked to poorer colon cancer patient survival (47), and MAM domain containing 4 (MAMDC4) was associated with the prognosis of esophageal adenocarcinoma (48). Cancer cells maintain low intracellular pH.…”

Section: Discussionmentioning

confidence: 99%

Enhanced expression of queuine tRNA-ribosyltransferase 1 (QTRT1) predicts poor prognosis in lung adenocarcinoma

Ma¹,

He²

2020

Ann Transl Med

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Background: Lung adenocarcinoma (LUAD) is the most frequently diagnosed type of lung cancer with high percentage of tumor relapse and metastasis. The correlation between queuine tRNA-ribosyltransferase 1 (QTRT1) expression and LUAD remains largely unknown. In this study, we aim to investigate the potential role of QTRT1 expression in the prognosis of LUAD.Methods: We abstracted data from The Cancer Genome Atlas (TCGA) and four independent Gene Expression Omnibus (GEO) datasets. In total, 1,012 LUAD samples and 112 normal tissue samples were selected. The relationship between QTRT1 expression, methylation, and clinical features in LUAD were determined, and bioinformatics analyses were also performed.Results: The expression of QTRT1 was higher in LUAD patients. A marked downregulation in QTRT1 methylation in LUAD was also found. Low QTRT1 expression was associated with longer overall survival across the GEO and TCGA datasets (P=0.0033, 0.0022, respectively). Furthermore, QTRT1 expression was significantly correlated with 'axoneme assembly', 'androgen response', and 'epithelial mesenchymal transition', as determined by Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) term enrichment analysis.Conclusions: QTRT1 was highly expressed in LUAD, and enhanced expression of QTRT1 might therefore serve as a biomarker for poor prognosis in LUAD. The result of bioinformatic analyses might present a new insight for investigating the pathogenesis of LUAD.

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In colonic ρ0 (rho0) cells reduced mitochondrial function mediates transcriptomic alterations associated with cancer

Cited by 10 publications

References 48 publications

Gut bacteria signaling to mitochondria in intestinal inflammation and cancer

Gut bacteria signaling to mitochondria in intestinal inflammation and cancer

Effect of mtDNA depletion from C6 glioma cells and characteristics of the generated C6ρ0 cells

Enhanced expression of queuine tRNA-ribosyltransferase 1 (QTRT1) predicts poor prognosis in lung adenocarcinoma

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