Evidence map›Paper›PMID 30389502›Full record

ArticleEBioMedicine2018

The antineoplastic drug metformin downregulates YAP by interfering with IRF-1 binding to the YAP promoter in NSCLC.

Dan Jin, Jiwei Guo, Deqiang Wang, Yan Wu, Xiaohong Wang, Yong Gao, Cuijie Shao, Xin Xu, Shuying Tan

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

17 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. mMolecular cancer · 2020
    Article
  10. Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis.Journal of experimental & clinical cancer research : CR · 2020
    Article
  11. Review
  12. Mechanisms of metformin inhibiting cancer invasion and migration.American journal of translational research · 2020
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Dan JinDepartment of Pain, Binzhou Medical University Hospital, Binzhou 256603, PR China.
Jiwei GuoCancer research institute, Binzhou Medical University Hospital, Binzhou 256603, PR China. Electronic address: guojiwei0510@163.com.
Deqiang WangDepartment of Pain, Binzhou Medical University Hospital, Binzhou 256603, PR China.
Yan WuCancer research institute, Binzhou Medical University Hospital, Binzhou 256603, PR China.
Xiaohong WangDepartment of Thyroid and Breast Surgery, Binzhou Medical University Hospital, Binzhou 256603, PR China.
Yong GaoDepartment of Pain, Binzhou Medical University Hospital, Binzhou 256603, PR China.
Cuijie ShaoDepartment of Pain, Binzhou Medical University Hospital, Binzhou 256603, PR China.
Xin XuDepartment of Pain, Binzhou Medical University Hospital, Binzhou 256603, PR China.
Shuying TanDepartment of Pain, Binzhou Medical University Hospital, Binzhou 256603, PR China.
Binzhou Medical University · CNBinzhou University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundActivation of the oncogene YAP has been shown to be related to lung cancer progression and associates with poor prognosis and metastasis. Metformin is a drug commonly used in the treatment of diabetes and with anticancer activity. However, the mechanism through which metformin inhibits tumorigenesis via YAP is poorly understood.

methodsThe mRNA and protein expressions were analyzed by RT-PCR and western blot. The cellular proliferation was detected by CCK8 and MTT. The cell migration and invasion growth were analyzed by wound healing assay and transwell assay. The activities of promoter were analyzed by luciferase reporter assay. Chromatin immunoprecipitation detected the combining ability of IRF-1 and 5'UTR-YAP.

findingsOur immunohistochemistry staining and RT-PCR assays showed that the expression of YAP was higher in lung carcinoma samples. Interestingly, metformin was able to downregulate YAP mRNA and protein expression in lung cancer cells. Mechanistically, we found that metformin depressed YAP promoter by competing with the binding of the transcription factor IRF-1 in lung cancer cells. Moreover, combination of metformin and verteporfin synergistically inhibits cell proliferation, promotes apoptosis and suppresses cell migration/invasion by downregulating YAP, therefore reduces the side effects caused by their single use and improve the quality of life for patients with lung cancer.

interpretationwe concluded that metformin depresses YAP promoter by interfering with the binding of the transcription factor IRF-1. Importantly, verteporfin sensitizes metformin-induced the depression of YAP and inhibition of cell growth and invasion in lung cancer cells. FUND: This work was supported by National Natural Science Foundation of China (No.31801085), the Science and Technology Development Foundation of Yantai (2015ZH082), Natural Science Foundation of Shandong Province (ZR2018QH004, ZR2016HB55, ZR2017PH067 and ZR2017MH125), and Research Foundation of Binzhou Medical University (BY2015KYQD29 and BY2015KJ14).

Indexed as

Promoter Regions, GeneticA549 CellsAdaptor Proteins, Signal TransducingAnimalsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungDown-RegulationFemaleGene Expression Regulation, NeoplasticHumansInterferon Regulatory Factor-1Lung NeoplasmsMetforminMiceMice, Inbred BALB CMice, NudeAdaptor Proteins, Signal TransducingAntineoplastic AgentsInterferon Regulatory Factor-1IRF1 protein, humanMetforminPhosphoproteinsTranscription FactorsYAP1 protein, humanYAP-Signaling ProteinsEMTIRF-1Lung cancerMetforminVerteporfinYAP

Identifiers

PMID30389502
PMCPMC6284514
OpenAlexW2898879934

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.