Promoter demethylation of nuclear factor-erythroid 2-related factor 2 gene in drug-resistant colon cancer cells

Zhao, Xiaoqian; Zhang, Yifei; Xia, Yifang; Zhou, Zhongmei; Cao, Ying-Qing

doi:10.3892/ol.2015.3468

Cited by 34 publications

(22 citation statements)

References 38 publications

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“…Under 5‐FU treatment, Nrf2 is translocated into CRC cell nucleus and interacts with the OH‐1 promoter region, inducing cellular protection. Together, these results highlight that upregulation of Nrf2 and HO‐1 expression by epigenetic DNA demethylation induces acquisition of 5‐FU resistance in CRC cells 73 …”

Section: Epigenetic Alterationsmentioning

confidence: 66%

5‐Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes

et al. 2020

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Colorectal cancer (CRC) is a public health problem. It is the third most common cancer in the world, with nearly 1.8 million new cases diagnosed in 2018. The only curative treatment is surgery, especially for early tumor stages. When there is locoregional or distant invasion, chemotherapy can be introduced, in particular 5‐fluorouracil (5‐FU). However, the disease can become tolerant to these pharmaceutical treatments: resistance emerges, leading to early tumor recurrence. Different mechanisms can explain this 5‐FU resistance. Some are disease‐specific, whereas others, such as drug efflux, are evolutionarily conserved. These mechanisms are numerous and complex and can occur simultaneously in cells exposed to 5‐FU. In this review, we construct a global outline of different mechanisms from disruption of 5‐FU‐metabolic enzymes and classic cellular processes (apoptosis, autophagy, glucose metabolism, oxidative stress, respiration, and cell cycle perturbation) to drug transporters and epithelial‐mesenchymal transition induction. Particular interest is directed to tumor microenvironment function as well as epigenetic alterations and miRNA dysregulation, which are the more promising processes that will be the subject of much research in the future.

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Section: Epigenetic Alterationsmentioning

confidence: 66%

5‐Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes

et al. 2020

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“…This in turn results in greater risk of CRC [35]. Other authors have observed similar results when NRF2 is overexpressed as a consequence of silencing, or as a result of epigenetic changes in this gene [36–38, 51]. Another way to induce overexpression of NRF2 is using chemical compounds.…”

Section: Discussionmentioning

confidence: 89%

The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review

et al. 2017

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BackgroundColorectal cancer is one of the most common cancers worldwide, and is influenced by the interplay of various factors, including a very strong genetic component. For instance, incorrect mitochondrial biogenesis is correlated with increased risk of developing colorectal cancer. Thus, it is important to understand the consequences of changes in both the expression and the correct function of the transcription factors that regulate mitochondrial biogenesis, namely NRF2.ObjectivesThe main objective of this paper is to characterise the relationship between NRF2 and colorectal cancer by compiling data from an exhaustive literature search.MethodsInformation was obtained by defining specific search terms and searching in several databases. After a strict selection procedure, data were tabulated and the relationships between articles were assessed by measuring heterogeneity and by constructing conceptual maps.Results and discussionWe found a general consensus in the literature that the presence of oxidizing agents as well as the inhibition of the NRF2 repressor Keap1 maintain NRF2 expression at basal levels. This predominantly exerts a cytoprotective effect on cells and decreases risk of colorectal cancer. However, if NRF2 is inhibited, protection against external agents disappears and risk of colorectal cancer increases. Interestingly, colorectal cancer risk is also increased when NRF2 becomes overexpressed. In this case, the increased risk arises from NRF2-induced inflammation and resistance to chemotherapy.ConclusionThe proper basal function of NRF2 and Keap1 are essential for preventing oncogenic processes in the colon. Consequently, any disruption to the expression of these genes can promote the genesis and progression of colon cancer.

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“…( 126 , 127 ) Stimulation of ABC transporters and multidrug resistance protein 2 (MDR2) by NRF2 facilitates the clearance of anticancer drugs, which in turn induces chemoresistance in cancer cells and promotes tumor growth. ( 128 , 129 ) Such cases have been reported clinically for several types of cancers. However, no report has shown that long-term intake of NRF2-stimulating compounds causes similar conditions.…”

Section: Negative Aspects Of Nrf2 Activation: Nrf2 As a Double-edged mentioning

confidence: 89%

Role of NRF2 in protection of the gastrointestinal tract against oxidative stress

Yanaka

2018

J. Clin. Biochem. Nutr.

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The gastrointestinal tract is exposed to a variety of noxious factors, such as Helicobacter pylori, nonsteroidal anti-inflammatory drugs, gastric acid, ischemia-reperfusion, and mental stresses. Theses stressors generate free radicals within gastrointestinal tissues, causing organ injury and functional disturbance. Although the gastrointestinal tract can withstand such oxidative stresses to some extent by enhancing its antioxidant system via nuclear factor erythroid 2-related factor 2-Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1-mediated pathways, acute or chronic exposure to oxidative stress can cause several gastrointestinal tract disorders, such as inflammation, ulcers, cancers, and various functional disturbances. Recent studies have demonstrated that some natural compounds and drugs can upregulate the nuclear factor erythroid 2-related factor 2-mediated antioxidant system, ameliorating or preventing these disorders. Although these compounds may be useful as chemopreventive agents, sufficient evidence for their clinical efficacy has not yet been provided. In addition, it is important to note that excessive nuclear factor erythroid 2-related factor 2 stimulation can be harmful to human health, especially from the standpoint of tumor biology.

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Promoter demethylation of nuclear factor-erythroid 2-related factor 2 gene in drug-resistant colon cancer cells

Cited by 34 publications

References 38 publications

5‐Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes

5‐Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes

The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review

Role of NRF2 in protection of the gastrointestinal tract against oxidative stress

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