ArticleApoptosis : an international journal on programmed cell death2023
DNMT2/TRDMT1 gene knockout compromises doxorubicin-induced unfolded protein response and sensitizes cancer cells to ER stress-induced apoptosis.
Article in Apoptosis : an international journal on programmed cell death, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 32 citations in OpenAlex.
- Protein arginine methylation and ubiquitination: A prominent crosstalk and its functions in cancer.Genes & diseases · 2026Review
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Epitranscriptomic control of cancer: the emerging roles of m⁵C and ac⁴C RNA modifications.Cell death discovery · 2026Review
- DNMT3A in cancer: from epigenetic writer to oncogenic driver.Clinical epigenetics · 2026Review
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- ATF6 Identification Sensitizes B-Cell Precursor Acute Lymphoblastic Leukemia Cells to Doxorubicin.Current medical science · 2026Article
- 5-mC RNA methylation: a key regulator in cancer development and treatment.Journal of translational medicine · 2026Review
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- Therapy-induced mRNA, rRNA and tRNA methylation alterations confer tolerance phenotype in tumor cells: mechanism and implications.International journal of biological sciences · 2026Review
- A systematic review on the potential of modulating the IRE arm of the UPR in U87 and U251 glioblastoma cells for improved therapeutic efficacy.Molecular biology research communications · 2026Review
- Cancer Cell Dormancy and Chemotherapy Resistance.Journal of Cancer · 2026Review
- Endoplasmic reticulum stress-mediated programmed cell death in the tumor microenvironment.Cell death discovery · 2025Review
- Targeting of miR-93-5p/Mfn2 Axis Attenuates Lung Fibrosis in Rats With Acute Respiratory Distress Syndrome by Regulating Endoplasmic Reticulum Stress.Physiological research · 2025Article
- Review
- DNMT Enzymes and Their Impact on Cervical Cancer: A State-of-the-Art Review.International journal of molecular sciences · 2025Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Gynecological Cancers: A Narrative Review.Cureus · 2025Review
- DNA-encoded library screening uncovers potent DNMT2 inhibitors targeting a cryptic allosteric binding site.iScience · 2025Article
- Association of TRDMT1 Gene Polymorphisms With Neuroblastoma Susceptibility: Insights From a Case-Control Study.Journal of cellular and molecular medicine · 2025Article
- TRDMT1 methyltransferase gene knockout attenuates STING-based cell death signaling during self-extracellular RNA-mediated response in drug-induced senescent osteosarcoma cells.Cellular and molecular life sciences : CMLS · 2025Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The acidic, hypoxic and nutrient-deprived tumor microenvironment may induce endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may exert an important cytoprotective role by promoting folding of newly synthesized proteins and cancer cell survival. The lack of DNMT2/TRDMT1 methyltransferase-mediated C38 tRNA methylation compromises translational fidelity that may result in the accumulation of misfolded and aggregated proteins leading to proteotoxic stress-related cell death. In the present study, DNMT2/TRDMT1 gene knockout-mediated effects were investigated during doxorubicin (DOX)-induced ER stress and PERK-, IRE1- and ATF6-orchestrated UPR in four genetically different cellular models of cancer (breast and cervical cancer, osteosarcoma and glioblastoma cells). Upon DOX stimulation, DNMT2/TRDMT1 gene knockout impaired PERK activation and modulated NSUN and 5-methylcytosine RNA-based responses and microRNA profiles. The lack of DNMT2/TRDMT1 gene in DOX-treated four cancer cell lines resulted in decreased levels of four microRNAs, namely, miR-23a-3p, miR-93-5p, miR-125a-5p and miR-191-5p involved in the regulation of several pathways such as ubiquitin-mediated proteolysis, amino acid degradation and translational misregulation in cancer. We conclude that DNMT2/TRDMT1 gene knockout, at least in selected cellular cancer models, affects adaptive responses associated with protein homeostasis networks that during prolonged ER stress may result in increased sensitivity to apoptotic cell death.
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