Impaired mitochondrial protein synthesis in head and neck squamous cell carcinoma

Koc, Emine C.; Hacıosmanoğlu, Ebru; Claudio, Pier Paolo; Wolf, Allison; Califano, Luigi; Friscia, Marco; Cortese, Antonio; Koç, Hasan

doi:10.1016/j.mito.2015.07.123

Cited by 29 publications

(20 citation statements)

References 48 publications

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“…These hub RBPs are mitochondrial ribosomal proteins that are essential for maintaining mitochondrial functions. Impaired mitochondrial functions such as apoptosis and oxidative phosphorylation are found in most cancers, however, their mechanisms are unclear (Koc et al, 2015;Lee et al, 2017;Lin et al, 2019). Lee et al (2017) found that suppressed MRPL13 expression increased hepatoma cell invasiveness.…”

Section: Discussionmentioning

confidence: 99%

“…Lee et al (2017) found that suppressed MRPL13 expression increased hepatoma cell invasiveness. Koc et al (2015) proposed that defects in mitochondrial function in head and neck squamous cell carcinoma might be caused by a decrease in MRPL11 expression. Shi et al (2015) revealed that MRPL21 was significantly overexpressed in esophageal squamous cell carcinoma (ESCC) and could be used as a candidate prognostic biomarker.…”

Section: Discussionmentioning

confidence: 99%

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Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Xue

Gao

et al. 2020

Front. Genet.

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Lung cancer is the leading cause of cancer-related deaths worldwide. Dysregulation of RNA binding proteins (RBPs) has been found in a variety of cancers and is related to oncogenesis and progression. However, the functions of RBPs in lung squamous cell carcinoma (LUSC) remain unclear. In this study, we obtained gene expression data and corresponding clinical information for LUSC from The Cancer Genome Atlas (TCGA) database, identified aberrantly expressed RBPs between tumors and normal tissue, and conducted a series of bioinformatics analyses to explore the expression and prognostic value of these RBPs. A total of 300 aberrantly expressed RBPs were obtained, comprising 59 downregulated and 241 upregulated RBPs. Functional enrichment analysis indicated that the differentially expressed RBPs were mainly associated with mRNA metabolic processes, RNA processing, RNA modification, regulation of translation, the TGF-beta signaling pathway, and the Toll-like receptor signaling pathway. Nine RBP genes (A1CF, EIF2B5, LSM1, LSM7, MBNL2, RSRC1, TRMU, TTF2, and ZCCHC5) were identified as prognosis-associated hub genes by univariate, least absolute shrinkage and selection operator (LASSO), Kaplan-Meier survival, and multivariate Cox regression analyses, and were used to construct the prognostic model. Further analysis demonstrated that high risk scores for patients were significantly related to poor overall survival according to the model. The area under the time-dependent receiver operator characteristic curve of the prognostic model was 0.712 at 3 years and 0.696 at 5 years. We also developed a nomogram based on nine RBP genes, with internal validation in the TCGA cohort, which showed a favorable predictive efficacy for prognosis in LUSC. Our results provide novel insights into the pathogenesis of LUSC. The nine-RBP gene signature showed predictive value for LUSC prognosis, with potential applications in clinical decision-making and individualized treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Xue

Gao

et al. 2020

Front. Genet.

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“…uL11m was considered a potential cancer biomarker when tissues from patients suffering from head and neck squamous cell carcinoma (HSNCC) presented altered expression of OXPHOS complexes and defective mitochondrial translation over the progression of HSNCC, associated with a decrease in MRPL11 expression [14]. This observation was in agreement with microarray analyses of HNSCC primary tumor tissues and cell lines and HN cancer cell lines showing that transcription of mitoribosomal genes MRPL11 and MRPL21 were aberrantly expressed in squamous cell carcinoma tissues [111].…”

Section: Mitoribosome Components As Biomarkers and Their Associatimentioning

confidence: 99%

“…Therefore, it is not surprising that gene expression studies have found alterations in the levels of mitoribosome proteins or assembly factors associated with the development of cancer [14, 15]. As a consequence, therapeutic approaches targeting mitochondrial protein synthesis have emerged as new interventions to combat specific types of malignancies [16–18].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial ribosomes in cancer

Kim

Maiti

Barrientos

2017

Seminars in Cancer Biology

146

120

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Mitochondria play fundamental roles in the regulation of life and death of eukaryotic cells. They mediate aerobic energy conversion through the oxidative phosphorylation (OXPHOS) system, and harbor and control the intrinsic pathway of apoptosis. As a descendant of a bacterial endosymbiont, mitochondria retain a vestige of their original genome (mtDNA), and its corresponding full gene expression machinery. Proteins encoded in the mtDNA, all components of the multimeric OXPHOS enzymes, are synthesized in specialized mitochondrial ribosomes (mitoribosomes). Mitoribosomes are therefore essential in the regulation of cellular respiration. Additionally, an increasing body of literature has been reporting an alternative role for several mitochondrial ribosomal proteins as apoptosis-inducing factors. No surprisingly, the expression of genes encoding for mitoribosomal proteins, mitoribosome assembly factors and mitochondrial translation factors is modified in numerous cancers, a trait that has been linked to tumorigenesis and metastasis. In this article, we will review the current knowledge regarding the dual function of mitoribosome components in protein synthesis and apoptosis and their association with cancer susceptibility and development. We will also highlight recent developments in targeting mitochondrial ribosomes for the treatment of cancer.

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“…In this regard, higher mitochondrial mass, increased mitobiogenesis, and translation were positively correlated with proliferating tissue compared with solid (stable) tumors, and in metastatic tumors, they correlated with recurrence and poor clinical outcome (Hüttemann et al , ). Gene expression studies have identified differential expression of mitochondrial ribosomes (mitoribosomes) genes in association with cancer development, and mitochondria have been proposed as key targets in cancer therapeutics (Järås and Ebert, ; Kim et al , ; Koc et al , ; Lamb et al , ; Wallace, ). In particular, more than 95 gene transcripts associated with mitochondrial biogenesis and/or translation were significantly upregulated in human epithelial breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Diabetes‐mediated promotion of colon mucosa carcinogenesis is associated with mitochondrial dysfunction

et al. 2019

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Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of cancer, including colon cancer (CC). However, we recently reported no influence of T2DM on CC prognosis, suggesting that any effect might be at the early stages of tumor development. We hypothesized that T2DM may create an environment in the healthy tissue, which acts as a carcinogenesis driver in agreement with the field of cancerization concept. Here, we focused on early carcinogenesis by analyzing paired tumor and normal colonic mucosa samples from the same patients. The proteome of CC and paired mucosa was quantitatively analyzed in 28 individuals (12 diabetics and 16 nondiabetics) by mass spectrometry with isobaric labeling. Out of 3076 identified proteins, 425 were differentially expressed at the tumor in diabetics compared with nondiabetics. In the adjacent mucosa, 143 proteins were differentially expressed in diabetics and nondiabetics. An enrichment analysis of this signature pointed to mitochondria, ribosome, and translation. Only six proteins were upregulated by diabetes both in tumor and mucosa, of which five were mitochondrial proteins. Differential expression in diabetic versus nondiabetic mucosa was confirmed for MRPL53, MRPL18, and TIMM8B. Higher levels of MRPL18, TIMM8B, and EIF1A were also found in normal colon epithelial cells exposed to high‐glucose conditions. We conclude that T2DM is associated with specific molecular changes in the normal mucosa of CC patients, consistent with field of cancerization in a diabetic environment. The mitochondrial protein signature identifies a potential therapeutic target that could underlie the higher risk of CC in diabetics.

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Impaired mitochondrial protein synthesis in head and neck squamous cell carcinoma

Cited by 29 publications

References 48 publications

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma

Mitochondrial ribosomes in cancer

Diabetes‐mediated promotion of colon mucosa carcinogenesis is associated with mitochondrial dysfunction

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