Evidence map›Paper›PMID 24743738›Full record

ArticleCell death & disease2014

Epigenetic modification of Nrf2 in 5-fluorouracil-resistant colon cancer cells: involvement of TET-dependent DNA demethylation.

K A Kang, M J Piao, K C Kim, H K Kang, W Y Chang, I C Park, Y S Keum, Y J Surh, J W Hyun

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.

  1. Pooled it
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  9. Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025
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26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

K A KangSchool of Medicine, Jeju National University, Jeju, Korea.
M J PiaoSchool of Medicine, Jeju National University, Jeju, Korea.
K C KimSchool of Medicine, Jeju National University, Jeju, Korea.
H K KangSchool of Medicine, Jeju National University, Jeju, Korea.
W Y ChangSchool of Medicine, Jeju National University, Jeju, Korea.
I C ParkDivision of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Y S KeumDepartment of Biochemistry, College of Pharmacy, Dongguk University, Goyang, Korea.
Y J SurhTumor Microenvironment Global Core Research Center and Cancer Research Institute, Seoul National University, Seoul, Korea.
J W HyunSchool of Medicine, Jeju National University, Jeju, Korea.
Jeju National University · KRDongguk University · KRKorea Institute of Radiological and Medical Sciences · KRSeoul National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

5-Fluorouracil (5-FU) is a widely used anticancer drug for the treatment of colorectal cancer (CRC). However, resistance to 5-FU often prevents the success of chemotherapy. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional regulator and a possible target to overcome 5-FU resistance. The present study examined epigenetic changes associated with Nrf2 induction in a human CRC cell line (SNUC5) resistant to 5-FU (SNUC5/5-FUR). Nrf2 expression, nuclear translocation, and binding to promoter were higher in SNUC5/5-FUR cells than in SNUC5 cells. The activated Nrf2 in SNUC5/5-FUR cells led to an increase in the protein expression and activity of heme oxygenase-1 (HO-1), an Nrf2-regulated gene. SNUC5/5-FUR cells produced a larger amount of reactive oxygen species (ROS) than SNUC5 cells. The siRNA- or shRNA-mediated knockdown of Nrf2 or HO-1 significantly suppressed cancer cell viability and tumor growth in vitro and in vivo, resulting in enhanced 5-FU sensitivity. Methylation-specific (MS) or real-time quantitative MS-PCR data showed hypomethylation of the Nrf2 promoter CpG islands in SNUC5/5-FUR cells compared with SNUC5 cells. Expression of the DNA demethylase ten-eleven translocation (TET) was upregulated in SNUC5/5-FUR cells. ROS generated by 5-FU upregulated TET1 expression and function, whereas antioxidant had the opposite effect. These results suggested that the mechanism underlying the acquisition of 5-FU resistance in CRC involves the upregulation of Nrf2 and HO-1 expression via epigenetic modifications of DNA demethylation.

Indexed as

AnimalsBiocatalysisCell Line, TumorColonic NeoplasmsDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDrug Resistance, NeoplasmEpigenesis, GeneticFluorouracilGene Knockdown TechniquesHeme Oxygenase-1HumansIntracellular SpaceMice, NudeMixed Function OxygenasesDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesFluorouracilHeme Oxygenase-1Mixed Function OxygenasesNF-E2-Related Factor 2Proto-Oncogene ProteinsReactive Oxygen SpeciesTET1 protein, human

Identifiers

PMID24743738
PMCPMC4001304
OpenAlexW1976150924

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.