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Hypermethylation at 45S rDNA promoter in cancers.
PLoS One
January 2025
Faculty of Biology, VNU University of Science, Vietnam National University, Hanoi, Vietnam.
The ribosomal genes (rDNA genes) encode 47S rRNA which accounts for up to 80% of all cellular RNA. At any given time, no more than 50% of rDNA genes are actively transcribed, and the other half is silent by forming heterochromatin structures through DNA methylation. In cancer cells, upregulation of ribosome biogenesis has been recognized as a hallmark feature, thus, the reduced methylation of rDNA promoter has been thought to support conformational changes of chromatin accessibility and the subsequent increase in rDNA transcription.
View Article and Find Full Text PDFTargeting mitochondrial RNAs enhances the efficacy of the DNA-demethylating agents.
Sci Rep
December 2024
Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
Hypomethylating agents (HMAs) such as azacytidine and decitabine are FDA-approved chemotherapy drugs for hematologic malignancy. By inhibiting DNA methyltransferases, HMAs reactivate tumor suppressor genes (TSGs) and endogenous double-stranded RNAs (dsRNAs) that limit tumor growth and trigger apoptosis via viral mimicry. Yet, HMAs show limited effects in many solid tumors despite the strong induction of TSGs and dsRNAs.
View Article and Find Full Text PDFLINE-1-Induced Retrotransposition Affects Early Preimplantation Embryo DNA Integrity and Pluripotency.
Int J Mol Sci
November 2024
Laboratory of Medical Genetics and Human Reproduction, School of Health Sciences, Faculty of Medicine, University of Ioannina, 451 10 Ioannina, Greece.
Retrotransposable elements are implicated in genome rearrangements and gene expression alterations that result in various human disorders. In the current study, we sought to investigate the potential effects of long interspersed elements-1 (LINE-1) overexpression on the integrity and methylation of DNA and on the expression of three major pluripotency factors (OCT4, SOX2, NANOG) during the preimplantation stages of human embryo development. Human MI oocytes were matured in vitro to MII and transfected through intracytoplasmic sperm injection (ICSI) either with an EGFP vector carrying a cloned active human LINE-1 retroelement or with the same EGFP vector without insert as control.
View Article and Find Full Text PDFBRCA1 & BRCA2 methylation as a prognostic and predictive biomarker in cancer: Implementation in liquid biopsy in the era of precision medicine.
Clin Epigenetics
December 2024
Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100, Alexandroupolis, Greece.
Article Synopsis
- BRCA1 and BRCA2 are tumor suppressor genes critical for repairing DNA damage through the Homologous Recombination pathway, and mutations in these genes are linked to higher risks of breast and ovarian cancers.
- Methylation of BRCA1/2 promoters can create a "BRCAness" phenotype, indicating HR deficiency in tumors, even when BRCA mutations are absent, and this methylation may serve as a valuable biomarker for predicting responsiveness to therapies like PARP inhibitors.
- The review emphasizes the need for further research into BRCA1/2 methylation as a predictive tool in cancer treatment, suggesting it could significantly enhance prognosis and treatment strategies across various cancer types.
Compound-dependent fetal toxicity after in utero exposure to chemotherapy in a pregnant mouse model.
Environ Toxicol Pharmacol
December 2024
Department of Oncology, KU Leuven, Leuven, Belgium; Department of Obstetrics and Gynecology, UZ Leuven, Leuven, Belgium; Gynecologic Oncology, Netherlands Cancer Institute, Anthony Van Leeuwenhoek, Amsterdam, the Netherlands. Electronic address:
Although chemotherapy is integrated in the treatment of second-trimester pregnant cancer patients, its potential cyto- and genotoxicity to fetal tissue remains unknown. To investigate any causal relation between in utero chemotherapy exposure and fetal toxicity, late-gestation pregnant BL6 mice were exposed to vehicle, or one of six chemotherapeutic compounds, used to treat pregnant cases: cyclophosphamide, carboplatin, cisplatin (alkylating agents), epirubicin, doxorubicin (anthracyclines) or paclitaxel (taxane). fetuses were euthanized at gestational day 18.
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