Evaluation of the Epigenetic Demethylation of NRF2, a Master Transcription Factor for Antioxidant Enzymes, in Colorectal Cancer

Taheri, Zahra; Aghdaei, Hamid Asadzadeh; Irani, Shiva; Modarressi, Mohammad Hossein; Noormohammadi, Zahra

doi:10.29252/rbmb.9.1.33

Cited by 16 publications

(8 citation statements)

References 32 publications

(23 reference statements)

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“…Kopke demonstrated that by administering antioxidants prior to noise exposure can lower hearing thresholds and prevent cell death (26). In this study, we found that administering 100 mg or 200 mg of curcumin for 14 days before noise exposure resulted in a significant difference in mean SNR values following DPOAE and NRF2 expression in all groups.…”

Section: Discussionsupporting

confidence: 48%

The Benefits of Curcuminoid to Expression Nuclear Factor Erythroid 2 Related Factor 2 (NRF2) and Signal to Noise Ratio (SNR) Value in the Noise Exposed Organ of Corti of Rattus Norvegicus

et al. 2021

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Background: Noise-induced hearing loss (NIHL) can cause damage to the cochlea. Curcumin and nuclear factor erythroid 2-related factor 2 (NRF2) are transcription activators that play a crucial role in defence mechanisms against oxidative stress. The aim of this study was to determine the effect of curcuminoid administration on NRF2 expression, in the organ of Corti of cochlea of Rattus norvegicus that were exposed to noise, from the results of the distortion product otoacoustic emission (DPOAE) examination. Methods: We divided 36 rats into six groups including Group 1 (control); Group 2 (noise exposure without curcuminoid administration); Group 3 (noise exposure+curcuminoid dose 100 mg/day for four days); Group 4 (noise exposure+curcuminoid dose 200 mg/day for four days); Group 5 (curcuminoid dose of 100 mg/day for 14 days followed by two days of noise exposure); Group 6 (curcuminoid dose 200 mg/day for 14 days followed by two days of noise exposure). Results: Following noise exposure in rats, there was an effect/correlation between NRF2 expression, the SNR values obtained from DPOAE and curcuminoid administration. Conclusions: There was a correlation between curcuminoid administration, NRF2 expression and DPOAE treatment. Following noise exposure in rats (Rattus norvegicus), SNR values obtained from DPOAE showed improved cochlear function.

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Section: Discussionsupporting

confidence: 48%

The Benefits of Curcuminoid to Expression Nuclear Factor Erythroid 2 Related Factor 2 (NRF2) and Signal to Noise Ratio (SNR) Value in the Noise Exposed Organ of Corti of Rattus Norvegicus

et al. 2021

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“…Epigenetics changes mean gene function cannot be explained by changes in DNA sequences (1). These changes are inherited and do not affect the DNA nucleotide sequence.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Decitabine Effects on HDAC3 and HDAC7 mRNA Expression in NALM-6 and HL-60 Cancer Cell Lines

et al. 2021

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Background: Decitabine is a potent anticancer hypomethylating agent and changes the gene expression through the gene's promoter demethylation and also independently from DNA demethylation. So, the present study was designed to distinguish whether Decitabine, in addition to inhibitory effects on DNA methyltransferase, can change HDAC3 and HDAC7 mRNA expression in NALM-6 and HL-60 cancer cell lines. Methods: HL-60, NALM-6, and normal cells were cultured, and the Decitabine treatment dose was obtained (1 µM) through the MTT assay. Finally, HDAC3 and HDAC7 mRNA expression were measured by Real-Time PCR in HL-60 and NALM-6 cancerous cells before and after treatment. Furthermore, HDAC3 and HDAC7 mRNA expression in untreated HL-60 and NALM-6 cancerous cells were compared to normal cells. Results: Our results revealed that the expression of HDAC3 and HDAC7 in HL-60 and NALM-6 cells increases as compared to normal cells. After treatment of HL-60 and NALM-6 cells with Decitabine, HDAC3, and HDAC7 mRNA expression were decreased significantly. Conclusions: Our data confirmed that the effects of Decitabine are not limited to direct hypomethylation of DNMTs, but it can indirectly affect other epigenetic factors, such as HDACs activity, through converging pathways.

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“…Conversely, demethylation of a CpG island in the promoter of NFE2L2 has been identified in CRC tumour samples. Whereas, the same site has been shown to be methylated in pre-cancerous colorectal polyps suggesting that the demethylation of NFE2L2 may influence carcinogenesis [271]. As KRAS and BRAF mutations are prevalent in CRC, NRF2 may frequently be upregulated by transcriptional activation of NFE2L2, as reported in mouse models of pancreatic cancer [164].…”

Section: Upregulation Of Nrf2 In Colorectal Tumoursmentioning

confidence: 97%

NRF2 and the Ambiguous Consequences of Its Activation during Initiation and the Subsequent Stages of Tumourigenesis

Robertson

Dinkova‐Kostova

Hayes

2020

Cancers

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NF-E2 p45-related factor 2 (NRF2, encoded in the human by NFE2L2) mediates short-term adaptation to thiol-reactive stressors. In normal cells, activation of NRF2 by a thiol-reactive stressor helps prevent, for a limited period of time, the initiation of cancer by chemical carcinogens through induction of genes encoding drug-metabolising enzymes. However, in many tumour types, NRF2 is permanently upregulated. In such cases, its overexpressed target genes support the promotion and progression of cancer by suppressing oxidative stress, because they constitutively increase the capacity to scavenge reactive oxygen species (ROS), and they support cell proliferation by increasing ribonucleotide synthesis, serine biosynthesis and autophagy. Herein, we describe cancer chemoprevention and the discovery of the essential role played by NRF2 in orchestrating protection against chemical carcinogenesis. We similarly describe the discoveries of somatic mutations in NFE2L2 and the gene encoding the principal NRF2 repressor, Kelch-like ECH-associated protein 1 (KEAP1) along with that encoding a component of the E3 ubiquitin-ligase complex Cullin 3 (CUL3), which result in permanent activation of NRF2, and the recognition that such mutations occur frequently in many types of cancer. Notably, mutations in NFE2L2, KEAP1 and CUL3 that cause persistent upregulation of NRF2 often co-exist with mutations that activate KRAS and the PI3K-PKB/Akt pathway, suggesting NRF2 supports growth of tumours in which KRAS or PKB/Akt are hyperactive. Besides somatic mutations, NRF2 activation in human tumours can occur by other means, such as alternative splicing that results in a NRF2 protein which lacks the KEAP1-binding domain or overexpression of other KEAP1-binding partners that compete with NRF2. Lastly, as NRF2 upregulation is associated with resistance to cancer chemotherapy and radiotherapy, we describe strategies that might be employed to suppress growth and overcome drug resistance in tumours with overactive NRF2.

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Evaluation of the Epigenetic Demethylation of NRF2, a Master Transcription Factor for Antioxidant Enzymes, in Colorectal Cancer

Cited by 16 publications

References 32 publications

The Benefits of Curcuminoid to Expression Nuclear Factor Erythroid 2 Related Factor 2 (NRF2) and Signal to Noise Ratio (SNR) Value in the Noise Exposed Organ of Corti of Rattus Norvegicus

The Benefits of Curcuminoid to Expression Nuclear Factor Erythroid 2 Related Factor 2 (NRF2) and Signal to Noise Ratio (SNR) Value in the Noise Exposed Organ of Corti of Rattus Norvegicus

Investigation of Decitabine Effects on HDAC3 and HDAC7 mRNA Expression in NALM-6 and HL-60 Cancer Cell Lines

NRF2 and the Ambiguous Consequences of Its Activation during Initiation and the Subsequent Stages of Tumourigenesis

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