Evidence map›Paper›PMID 31884422›Full record

ArticleAging2019

Genome-wide global identification of NRF2 binding sites in A549 non-small cell lung cancer cells by ChIP-Seq reveals NRF2 regulation of genes involved in focal adhesion pathways.

Akhileshwar Namani, Kaihua Liu, Shengcun Wang, Xihang Zhou, Yijiao Liao, Hongyan Wang, Xiu Jun Wang, Xiuwen Tang

Open access · greenAbstract read
In one paragraph

Article in Aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

22 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. ChIP-seq identifiesFrontiers in physiology · 2023
    Article
  10. Article
  11. DnaJC7 in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022
    Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Nrf2 in Cancer, Detoxifying Enzymes and Cell Death Programs.Antioxidants (Basel, Switzerland) · 2021
    Review
  18. Review
  19. Article
  20. Review
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

8 authors at 3 institutions in 1 country.

Akhileshwar NamaniDepartment of Biochemistry and Department of Thoracic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
Kaihua LiuDepartment of Pharmacology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
Shengcun WangDepartment of Biochemistry and Department of Thoracic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
Xihang ZhouDepartment of Biochemistry and Department of Thoracic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
Yijiao LiaoDepartment of Biochemistry and Department of Thoracic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
Hongyan WangDepartment of Biochemistry and Department of Thoracic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
Xiu Jun WangDepartment of Pharmacology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, PR China.
Xiuwen TangDepartment of Biochemistry and Department of Thoracic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
First Affiliated Hospital Zhejiang University · CNSecond Affiliated Hospital of Zhejiang University · CNZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nuclear factor erythroid-derived-2-like 2(NRF2) regulates its downstream genes through binding with antioxidant responsive elements in their promoter regions. Hyperactivation of NRF2 results in oncogenesis and drug resistance in various cancers including non-small cell lung cancer (NSCLC). However, identification of the genes and pathways regulated by NRF2 in NSCLC warrants further investigation. We investigated the global NRF2 genomic binding sites using the high-throughput ChIP-Seq technique in KEAP1 (Kelch-like ECH-associated protein 1)-mutated A549 (NSCLC) cells. We next carried out an integrated analysis of the ChIP-Seq data with transcriptomic data from A549 cells with NRF2-knockdown and RNA-Seq data from TCGA patients with altered KEAP1 to identify downstream and clinically-correlated genes respectively. Furthermore, we applied transcription factor enrichment analysis, generated a protein-protein interaction network, and used kinase enrichment analysis. Moreover, functional annotation of NRF2 binding sites using DAVID v7 identified the genes involved in focal adhesion. Putative focal adhesion genes regulated by NRF2 were validated using qRT-PCR. Further, we selected one novel conserved focal adhesion gene regulated by NRF2-LAMC1 (laminin subunit gamma 1) and validated it using a reporter assay. Overall, the identification of NRF2 target genes paves the way for identifying the molecular mechanism of NRF2 signaling in NSCLC development and therapy. Moreover, our data highlight the complexity of the pathways regulated by NRF2 in lung tumorigenesis.

Indexed as

Chromatin Immunoprecipitation SequencingGenome-Wide Association StudyA549 CellsBase SequenceCarcinoma, Non-Small-Cell LungDatabases, GeneticFocal AdhesionsGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansNF-E2-Related Factor 2Oligonucleotide Array Sequence AnalysisProtein BindingSignal TransductionNFE2L2 protein, humanNF-E2-Related Factor 2ChIP-seqfocal adhesionmicroarraynon-small-cell lung cancernuclear factor erythroid-derived-2-like 2

Identifiers

PMID31884422
PMCPMC6949066
OpenAlexW2997494150

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.