Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma

Lin, Ching-Heng; Wang, Liang Shun; Chang, Shi Chuan; Chou, Teh Ying; Hsu, Wen Hu; Liu, Chin San; Lee, Mau Hwa; Chung, Ming Yi; Wei, Yau‐Huei

doi:10.3892/or.2012.1761

Cited by 3 publications

(2 citation statements)

References 46 publications

(47 reference statements)

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“…During the past 20 years, alterations of mtDNA copy number in several human cancers had been extensively investigated [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 34 , 35 ]. Simonnet et al and Meierhofer et al demonstrated a decrease of mtDNA copy number and a decline of mitochondrial enzyme activity in human RCC and such a decrease was associated with the aggressiveness of RCC [ 29 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Alterations of mtDNA copy numbers in human cancers have been extensively studied [ 15 , 16 , 17 ]. An increase of the mtDNA copy number was noted in head and neck cancers, or esophageal squamous cell carcinoma, especially cigarette smokers [ 18 , 19 , 20 , 21 , 22 ]. Such an increase was supposed to compensate for the damaged mtDNA to keep the supply of ATP by mitochondrial respiration above a threshold.…”

Section: Introductionmentioning

confidence: 99%

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Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma

Lin

Lee

et al. 2016

IJMS

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We investigated the role of mitochondrial DNA (mtDNA) copy number alteration in human renal cell carcinoma (RCC). The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR). An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM). Null target (NT) and TFAM-knockdown (TFAM-KD) represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1), ND6 and cytochrome c oxidase subunit 2 (COX-2); nuclear DNA (nDNA)-encoded succinate dehydrogenase subunit A (SDHA); v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC)-encoded MYC; glycolytic enzymes including hexokinase II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), and lactate dehydrogenase subunit A (LDHA); and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase E1 component α subunit (PDHA1) were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB) and basal extracellular acidification rate (ECARB), were measured by a Seahorse XFe-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043). The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034), lower mRNA levels of TFAM (p = 0.008), ND1 (p = 0.007), and ND6 (p = 0.017), and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0.007); and drug resistance to doxorubicin (p = 0.008) of the TFAM-KD clone were significantly higher than those of the NT clone. Bioenergetically, the TFAM-KD clone expressed lower mOCRB (p = 0.009) but higher ECARB (p = 0.037) than did the NT clone. We conclude that a reduction of mtDNA copy number and decrease of respiratory function of mitochondria in RCC might be compensated for by an increase of enzymes and factors that are involved in the upregulation of glycolysis to confer RCC more invasive and a drug-resistant phenotype in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma

Lin

Lee

et al. 2016

IJMS

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Dynamic Changes of Mitochondrial DNA Copy Number in Gastrointestinal Tract Cancers: A Systematic Review and Meta-Analysis

Alikhani

Touati

Karimipoor

et al. 2021

Cancer Investigation

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Research highlights on contributions of mitochondrial DNA microsatellite instability in solid cancers – an overview

Yusoff¹,

Radzak²,

Khair³

2022

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Cancer has been broadly considered a genetic disease involving mutations in nuclear DNA and the mitochondrial genome (mtDNA). Mitochondria are essential bioenergetics and biosynthetic machinery found in most eukaryotic organisms. Thus, failure of their function is crucial for tumourigenesis, tumour cell growth, and metastasis. Mitochondrial dysregulation can occur as a consequence of molecular alterations in mtDNA, such as point mutations, deletions, inversions, microsatellite instability (MSI), and copy number variations. This review article aims to highlight the published research work on alterations in mtDNA, with a particular focus on mitochondrial MSI (mtMSI) in various types of solid cancers. Databases including PubMed, Scopus, and Google Scholar were searched for articles about mtMSI and its link to solid cancer published from 1990 till 2021. In this review, we briefly summarize the knowledge related to possible molecular mechanisms causing mtMSI formation and the available information on mtMSI frequency values in all main solid cancer types. Mutations in the mitochondrial genome are widely believed to have a broad impact across various cancers. Based on the available published data, mtMSI can act as a vital risk factor and a potential marker for cancer progression. Further research is required to unravel the role of mtMSI in tumourigenesis.

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Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma

Cited by 3 publications

References 46 publications

Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma

Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma

Dynamic Changes of Mitochondrial DNA Copy Number in Gastrointestinal Tract Cancers: A Systematic Review and Meta-Analysis

Research highlights on contributions of mitochondrial DNA microsatellite instability in solid cancers – an overview

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