ArticleJournal of translational medicine2022
Low mitochondrial DNA copy number induces chemotherapy resistance via epithelial-mesenchymal transition by DNA methylation in esophageal squamous cancer cells.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Three-Course Neoadjuvant Chemotherapy Associated with Unfavorable Survival of Non-responders to the First Two Courses for Locally Advanced Esophageal Cancer.Annals of surgical oncology · 2023Trial
- Mitochondrial function meets oncology: the multifaceted role of TFAM across cancer types.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
- Immunosuppressive tumor microenvironment and immunotherapy resistance of esophageal carcinoma.Frontiers in immunology · 2026Review
- Revealing the landscape of targeting mitochondrial functions and behaviors to overcome cancer chemoresistance.Journal of the National Cancer Center · 2025Review
- Mitochondrial metabolic reprogramming in colorectal cancer: mechanisms of resistance and future clinical interventions.Cell death discovery · 2025Review
- The Role of Mitochondrial DNA in Modulating Chemoresistance in Esophageal Cancer: Mechanistic Insights and Therapeutic Potential.Biomolecules · 2025Review
- Metastatic hepatic carcinoma: Mechanisms, emerging therapeutics, and future perspectives.iScience · 2025Review
- Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review).Molecular medicine reports · 2025Review
- Role of Hypoxia-Associated Long Noncoding RNAs in Cancer Chemo-Therapy Resistance.International journal of molecular sciences · 2025Review
- Novel mtDNA methylation-associated prognostic signatures in colorectal cancer.Frontiers in oncology · 2025Article
- D-loop mutations in mitochondrial DNA are a risk factor for chemotherapy resistance in esophageal cancer.Scientific reports · 2024Article
- Epigenetic reprogramming in gastrointestinal cancer: biology and translational perspectives.MedComm · 2024Review
- Epigenetics: Mechanisms, potential roles, and therapeutic strategies in cancer progression.Genes & diseases · 2024Review
- The Role of Mitochondrial Copy Number in Neurodegenerative Diseases: Present Insights and Future Directions.International journal of molecular sciences · 2024Review
- Mitochondrial DNA as a target for analyzing the biodistribution of cell therapy products.Scientific reports · 2024Article
- Leveraging new methods for comprehensive characterization of mitochondrial DNA in esophageal squamous cell carcinoma.Genome medicine · 2024Article
- Ovarian cancer cells regulate their mitochondrial content and high mitochondrial content is associated with a poor prognosis.BMC cancer · 2024Article
- Linc01614 Regulates the Proliferation, Apoptosis, and Chemotherapy Resistance in Esophageal Squamous Cell Carcinoma by Targeting Mir-4775.Iranian journal of public health · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEsophageal squamous cell carcinoma (ESCC) is one of the most severe cancers and is characterized by chemotherapy resistance and poor prognosis associated with epithelial-mesenchymal transition (EMT). In a previous study, a low mitochondrial DNA (mtDNA) copy number was associated with poorer prognosis and induced EMT in ESCC. However, the detailed mechanism related to mtDNA copy number and EMT is unclear. The aim of this study was to clarify the mechanism by which a change in mtDNA copy number contributes to EMT and to examine treatment of chemotherapy resistance in ESCC.
methodsThe association between low mtDNA copy number and chemotherapy resistance was investigated using specimens from 88 patients who underwent surgery after neoadjuvant chemotherapy. Then, the mtDNA content of human ESCC cell lines, TE8 and TE11, was depleted by knockdown of mitochondrial transcription factor A expression. The present study focused on modulation of mitochondrial membrane potential (MMP) and DNA methylation as the mechanisms by which mtDNA copy number affects EMT. mRNA and protein expression, chemotherapy sensitivity, proliferation, MMP and DNA methylation were evaluated, and in vitro and in vivo assays were conducted to clarify these mechanisms.
resultsESCC patients with decreased mtDNA copy number who underwent R0 resection after neoadjuvant chemotherapy had significantly worse pathological response and recurrence-free survival. Additionally, low mtDNA copy number was associated with resistance to chemotherapy in vitro and in vivo. mtDNA controlled MMP, and MMP depolarization induced EMT. Depletion of mtDNA and low MMP induced DNA methylation via a DNA methylation transcription factor (DNMT), and a DNMT inhibitor suppressed EMT and improved chemotherapy sensitivity in mtDNA-depleted ESCC cells, as shown by in vitro and in vivo assays.
conclusionThis study showed that decreased mtDNA copy number induced EMT via modulation of MMP and DNA methylation in ESCC. Therapeutic strategies increasing mtDNA copy number and DNMT inhibitors may be effective in preventing EMT and chemosensitivity resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.