Fusaric Acid-Induced Epigenetic Modulation of Hepatic H3K9me3 Triggers Apoptosis in Vitro and in Vivo

Abstract

Aim: To determine the effect of the food-borne mycotoxin, fusaric acid (FA) on miR-200a, SUV39H1-mediated H3K9me3, genome integrity and apoptosis in human liver (HepG2) cells and C57BL/6 mice livers. Materials & methods: MiR-200a, Sirt1, SUV39H1-mediated H3K9me3, genome integrity and apoptosis was measured in HepG2 cells and C57BL/6 mice livers using qPCR, western blot, DNA electrophoresis and luminometry. Results: FA: upregulated miR-200a and decreased Sirt1 expression in HepG2 cells and mice livers; decreased expression of SUV39H1 and KDM4B, thus decreasing H3K9me3 and increasing H3K9me1; increased cell mortality via apoptosis. Conclusion: FA induced apoptosis by upregulating miR-200a and decreasing SUV39H1-mediated H3K9me3 in HepG2 cells and mice livers.

Graphical abstract

Keywords::

• apoptosis
• fusaric acid
• genome instability
• H3K9me1
• H3K9me3
• KDM4B
• MiR-200a
• p-S139-H2Ax
• Sirt1
• SUV39H1

Supplementary data

To view the supplementary data that accompany this article please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0284

Acknowledgments

The authors would like to thank the Africa Health Research Institute for allowing us to use their animal housing facilities. We also thank S Singh and S Baijnath for their role in maintaining, treating and sacrificing the mice.

Financial & competing interests disclosure

This work was supported by the National Research Foundation (Grant no.: SFH160703175722) and the University of KwaZulu-Natal College of Health Sciences (Grant no.: 570869). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. All procedures involving the mice were performed according to the ARRIVE guidelines and rules and regulations of the University of KwaZulu-Natal Animal Research Ethics Committee (Ethics approval number: AREC/079/016).

Data availability

All datasets generated in this study are available in Supplementary Information and from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the National Research Foundation (Grant no.: SFH160703175722) and the University of KwaZuluNatal College ofHealth Sciences (Grant no.: 570869). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript