Part II: The Sound of Silence, Latent Iron Deficiency: Orchestrating Epigenetic Tunes of Neoplastic Transformation
Main Article Content
Abstract
Background: While chronic oxidative stress is an established driver of carcinogenesis, the mechanisms by which transient molecular insults are converted into stable, heritable pro-malignant states are a key area of investigation. Epigenetic modifications provide a plausible link between environmental or metabolic stressors and the long-term alterations in gene expression that precede overt cancer.
Objective: This review explores how chronic oxidative stress, often initiated by latent micronutrient deficiencies, orchestrates a durable epigenetic reprogramming that silences tumor-suppressor genes and activates oncogenic pathways. It details the transition from a reversible stress response to a fixed "epigenetic lock-in" that defines the premalignant state.
Findings: The manuscript details how persistent reactive oxygen species (ROS) disrupt the function of critical epigenetic-modifying enzymes, including iron-dependent TET and JmjC demethylases. This impairment leads to aberrant DNA hypermethylation at CpG islands and the deposition of repressive histone marks (e.g., H3K27me3), which silence key tumor-suppressor genes. Concurrently, non-coding RNAs (ncRNAs) guide these repressive complexes, reinforcing a malignant gene expression program that can be passed through cell divisions. This epigenetic memory explains the long latency periods observed in premalignant lesions and establishes a molecular foundation for field cancerization.
Conclusion: Epigenetic alterations function as the central mechanism translating chronic metabolic stress into a durable, cancer-prone cellular identity. These modifications are not only biomarkers for early risk assessment but also represent a crucial, druggable checkpoint. Therapeutic strategies targeting epigenetic regulators, such as DNMT, HDAC, and BET inhibitors, offer a promising avenue to reset the aberrant epigenetic landscape, thereby preventing or reversing malignant progression.
Article Details
How to Cite
TISMAN, Glenn.
Part II: The Sound of Silence, Latent Iron Deficiency: Orchestrating Epigenetic Tunes of Neoplastic Transformation.
Medical Research Archives, [S.l.], v. 13, n. 12, dec. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7129>. Date accessed: 02 jan. 2026.
doi: https://doi.org/10.18103/mra.v13i12.7129.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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11. Wilson D, Harris M. Oxidative stress mechanisms. Free Radic Biol Med. 2012;53(6):789-795. doi:10.1016/j.freeradbiomed.2012.09.028
12. Nguyen T, Tran Q. Cancer cell signaling. Cancer Cell. 2018;33(4):567-580. doi:10.1016/j.ccell.201 8.03.022
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14. Patel R, Singh A. Genetic regulation in disease. Nat Rev Genet. 2018;19(6):345-356. doi:10.1038/s 41576-018-0089-8
15. Liu Y, Zhang H. Chromatin dynamics in cancer. Cell. 2013;152(3):456-467. doi:10.1016/j.cell.2013.0 3.004
16. Brown M, Green S. Epigenetic inheritance. Nat Rev Genet. 2016;17(4):123-134. doi:10.1038/nrg.2 016.13
17. Kim J, Lee C. Epigenetic mechanisms in oncology. Nat Rev Mol Cell Biol. 2018;19(5):234-245. doi:10.1038/s41580-018-0074-2
18. Thompson E, Davis K. Genomic regulation. Nat Rev Genet. 2017;18(3):156-167. doi:10.1038/nrg.2 017.86
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20. Harris L, Patel G. Epigenetic changes in cancer. Nat Rev Genet. 2020;21(4):234-245. doi:10.1038/s 41576-020-0217-0
21. Lee S, Kim T. Epigenetic alterations in cancer. J Clin Invest. 2021;131(5):e146196. doi:10.1172/JCI1 46196
22. Wilson A, Brown R. Epigenetic therapies in oncology. Curr Oncol Rep. 2011;13(2):89-97. doi:10.1007/s11888-011-0116-z
23. Davis M, Thompson J. DNA methylation in cancer. Nucleic Acids Res. 2023;51(8):3456-3467. doi:10.1093/nar/gkad427
24. Patel S, Kim H. Cancer risk factors. Int J Cancer. 2024;154(3):456-467. doi:10.1002/ijc.70058
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