Fumonisin B1 alters global m6A RNA methylation and epigenetically regulates Keap1-Nrf2 signaling in human hepatoma (HepG2) cells

Arumugam, Thilona; Ghazi, Terisha; Chuturgoon, Anil A.

doi:10.1007/s00204-021-02986-5

Cited by 33 publications

(18 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numbers of research has revealed that 5-aza-2′-deoxycytidine (5-aza) treatment demethylated the CpG sites in the KEAP1 promoter region, synergistically contributing to KEAP1 overexpression, NRF2 degradation and inactivation of various relevant signal pathways ( Wang et al, 2008b ; Guo et al, 2015c ; Gao et al, 2019 ), which were related to enhanced survival and reduced lymph node metastasis of NSCLC patients ( Chien et al, 2015 ). Contrary to 5-aza, Fumonisin B, a common toxic mycotoxins of cereal grains, activated NRF2/KEAP1 pathway by hypermethylating CpG islands in KEAP1 gene, consequently enhancing ROS production along with promoting cell membrane damage in human hepatoma cells ( Arumugam et al, 2021 ). In conclusion, the expression and activation of KEAP1 could be regarded as an effective therapeutic strategy for advanced human cancers.…”

Section: Therapeutic Strategies Targeting Epigenetic Modifications Of...mentioning

confidence: 99%

Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress

et al. 2022

View full text Add to dashboard Cite

The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) and its negative regulator kelch-like ECH-associated protein 1 (KEAP1) regulate various genes involved in redox homeostasis, which protects cells from stress conditions such as reactive oxygen species and therefore exerts beneficial effects on suppression of carcinogenesis. In addition to their pivotal role in cellular physiology, accumulating innovative studies indicated that NRF2/KEAP1-governed pathways may conversely be oncogenic and cause therapy resistance, which was profoundly modulated by epigenetic mechanism. Therefore, targeting epigenetic regulation in NRF2/KEAP1 signaling is a potential strategy for cancer treatment. In this paper, the current knowledge on the role of NRF2/KEAP1 signaling in cancer oxidative stress is presented, with a focus on how epigenetic modifications might influence cancer initiation and progression. Furthermore, the prospect that epigenetic changes may be used as therapeutic targets for tumor treatment is also investigated.

show abstract

Section: Therapeutic Strategies Targeting Epigenetic Modifications Of...mentioning

confidence: 99%

Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Dietary phytochemicals have been demonstrated to have the potential to regulate Nrf2 expression by modulating m6A modification. As shown in Figure 6 , m6A-Nrf2 RNA methylation was related to upregulation of YTHDF1-3 and YTHDC2 and downregulation of ALKBH5 and FTO in HepG2 human hepatoma cells [ 135 ]. Furthermore, EGCG could inhibit the generation of FTO and promote the production of YTHDF2 in 3T3-L1 cells [ 136 ], and genistein could facilitate the expression of “eraser,” ALKBH5, in mice kidney [ 137 ].…”

Section: Potential M6a Modification Of Nrf2 Modulated By Dietary Phyt...mentioning

confidence: 99%

Dietary Phytochemicals Targeting Nrf2 to Enhance the Radiosensitivity of Cancer

Wang

Long

Lin

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Nowadays, cancer has become the second leading cause of death worldwide. Radiotherapy (RT) is the mainstay in management of carcinoma; however, overcoming radioresistance remains a great challenge to successfully treat cancer. Nrf2 is a key transcription factor that is responsible for maintaining cellular redox homeostasis. Activation of Nrf2 signaling pathway could upregulate multifarious antioxidant and detoxifying enzymes, further scavenging excessive reactive oxygen species (ROS). Despite its cytoprotective roles in normal cells, it could also alleviate oxidative stress and DNA damage caused by RT in cancer cells, thus promoting cancer cell survival. Accumulating evidence indicates that overactivation of Nrf2 is associated with radioresistance; therefore, targeting Nrf2 is a promising strategy to enhance radiosensitivity. Dietary phytochemicals coming from natural products are characterized by low cost, low toxicity, and general availability. Numerous phytochemicals are reported to regulate Nrf2 and intensify the killing capability of RT through diverse mechanisms, including promoting oxidative stress, proapoptosis, and proautophagy as well as inhibiting Nrf2-mediated cytoprotective genes expression. This review summarizes recent advances in radiosensitizing effects of dietary phytochemicals by targeting Nrf2 and discusses the underlying mechanisms, including N6-methyladenosine (m6A) modification of Nrf2 mediated by phytochemicals in cancer.

show abstract

“…FB1 also causes methylation of RNA, which is due to elevation of N6 methyladenosine (m6A). Meanwhile, hypermethylation of the kelch-like ECH associated protein 1 (Keap1) promoter and hypomethylation of the related factor 2 (Nrf2) promoter, a decrease in mir-27b, and an increase in m6a-keap1 and m6a-nrf2 also lead to the activation of the keap1-nrf2 signaling pathway [ 68 ].…”

Section: Toxic Mechanism Of Fb1mentioning

confidence: 99%

Research Progress on Fumonisin B1 Contamination and Toxicity: A Review

et al. 2021

View full text Add to dashboard Cite

Fumonisin B1 (FB1), belonging to the member of fumonisins, is one of the most toxic mycotoxins produced mainly by Fusarium proliferatum and Fusarium verticillioide. FB1 has caused extensive contamination worldwide, mainly in corn, rice, wheat, and their products, while it also poses a health risk and is toxic to animals and human. It has been shown to cause oxidative stress, endoplasmic reticulum stress, cellular autophagy, and apoptosis. This review focuses on the current stage of FB1 contamination, its toxic effects of acute toxicity, immunotoxicity, organ toxicity, and reproductive toxicity on animals and humans. The potential toxic mechanisms of FB1 are discussed. One of the main aims of the work is to provide a reliable reference strategy for understanding the occurrence and toxicity of FB1.

show abstract

Fumonisin B1 alters global m6A RNA methylation and epigenetically regulates Keap1-Nrf2 signaling in human hepatoma (HepG2) cells

Cited by 33 publications

References 56 publications

Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress

Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress

Dietary Phytochemicals Targeting Nrf2 to Enhance the Radiosensitivity of Cancer

Research Progress on Fumonisin B1 Contamination and Toxicity: A Review

Contact Info

Product

Resources

About