An extensive study conducted by researchers from the Discipline of Medical Biochemistry and Chemical Pathology, School of Laboratory Medicine and Medical Science, College of Health Sciences at the University of Kwa-Zulu Natal, South Africa, revealed that fusaric acid (FA), a mycotoxin prevalent in maize, plays a role in global DNA hypomethylation in human hepatocellular carcinoma (HepG2) cells. Published in the journal “Epigenetics” in August 2019, the research highlights the potential epigenetic mechanisms through which FA may exert toxicity in plants and animals, including humans.
In the study titled “Fusaric acid-induced promoter methylation of DNA methyltransferases triggers DNA hypomethylation in human hepatocellular carcinoma (HepG2) cells” (DOI: 10.1080/15592294.2019.1615358), the authors investigated the effect of FA on global DNA methylation as well as the transcriptional, post-transcriptional, and post-translational regulation of DNA methyltransferases (DNMTs; DNMT1, DNMT3A, and DNMT3B) and demethylases (MBD2) in HepG2 cells.
DNA methylation is a crucial epigenetic modification that shapes the genome structure and function, playing a significant role in various biological processes, including gene expression and the onset of cancer. Changes in the expression of enzymes that dictate the DNA methylation pattern, such as DNMTs and demethylases, are indicative of novel pathways through which toxins like FA can influence genetic regulation and contribute to disease.
Fusaric acid’s impact was pinpointed particularly on promoter methylation, microRNAs (miR-29b), and protein ubiquitination, mechanisms that are essential in maintaining DNA methylation homeostasis. The study found a reduction in global methylation levels, also known as DNA hypomethylation, which is recognized as a hallmark of many cancer types, including hepatocellular carcinoma.
Professor Anil A. Chuturgoon and his team utilized state-of-the-art molecular techniques to unriddle the complexity of how FA manipulates the epigenetic machinery. Their results include a downregulation of DNMT1 and DNMT3B through increased promoter methylation, paralleled by a rise in the levels of miR-29b—an antagonist RNA molecule known to impair DNMTs’ functionality. Furthermore, the ubiquitination processes involving UHRF1 and USP7, which typically help stabilize DNMTs, were also disrupted.
The implications of this research are far-reaching, as it offers a new understanding of mycotoxin-mediated cellular transformation that could lead to cancer. The potential health risks extend beyond those who directly consume contaminated products, considering the ubiquity of maize in global food supplies and its use as animal feed.
For the scientific community, this research paves the way for further investigations into fusaric acid’s role in cancer development. The findings may facilitate the design of novel diagnostic tools or therapies aimed at counteracting FA’s detrimental epigenetic effects. From a regulatory perspective, there may be implications for food safety standards with a focus on controlling FA levels in crops.
This scholarly article by Ghazi Terisha T., Nagiah Savania S., Naidoo Pragalathan P., and Chuturgoon Anil A. contributes significantly to the existing literature on mycotoxins and epigenetics. Their meticulous work serves as a stepping stone for future studies on FA and its impact on human health, specifically in relation to liver cancer.
Keywords
1. Fusaric acid DNA methylation
2. Hepatocellular carcinoma epigenetics
3. Mycotoxin impact on human cells
4. DNA methyltransferases regulation
5. Cancer DNA hypomethylation
As the scientific endeavor continues to uncover the mysteries of epigenetic mechanisms, studies such as this underscore the intricate interplay between environmental contaminants and genetic regulation. The potential for this research to influence public health policy, agricultural practices, and therapeutic interventions underscores the critical nature of understanding such intricate biological processes.
References
1. Ghazi Terisha T., Nagiah Savania S., Naidoo Pragalathan P., Chuturgoon Anil A. (2019). Fusaric acid-induced promoter methylation of DNA methyltransferases triggers DNA hypomethylation in human hepatocellular carcinoma (HepG2) cells. Epigenetics, 14(8), 804-817. DOI: 10.1080/15592294.2019.1615358
2. Bacon C., Porter J., Norred W., et al. (1996). Production of fusaric acid by Fusarium species. Applied and Environmental Microbiology, 62(11), 4039-4043. PMID: 8899996; PMC168225
3. Streit E., Schwab C., Sulyok M., et al. (2013). Multi-mycotoxin screening reveals the occurrence of 139 different secondary metabolites in feed and feed ingredients. Toxins (Basel), 5(3), 504-523. PMID: 23529186; PMC3705275
4. Singh VK., Singh HB., Upadhyay RS. (2017). Role of fusaric acid in the development of Fusarium wilt symptoms in tomato: physiological, biochemical and proteomic perspectives. Plant Physiology and Biochemistry, 118, 320-332. PMID: 28683401
5. Diniz S., Oliveira R. (2009). Effects of fusaric acid on Zea mays L. seedlings. Phyton – International Journal of Experimental Botany, 78, 155-160.
Article Conclusion
The groundbreaking insights gained from this study encourage deeper examination into the epigenetic impact of environmental contaminants. With fusaric acid being shown to deregulate pivotal mechanisms like DNA methylation, it is evident that there is a clear link between our environment and genetic stability. Such connections have the potential not only to elucidate the pathogenesis of diseases, such as liver cancer but also to promote the development of proactive strategies to mitigate exposure risks and safeguard human health.