Evidence map›Paper›PMID 29207128›Full record

ArticleInternational journal of oncology2018

NR4A1-induced increase in the sensitivity of a human gastric cancer line to TNFα-mediated apoptosis is associated with the inhibition of JNK/Parkin-dependent mitophagy.

Hongzhu Yan, Feng Xiao, Jue Zou, Chengmin Qiu, Weiwei Sun, Minmin Gu, Li Zhang

RetractedOpen access · hybridAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of oncology, 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 It has been retracted, and should not be counted.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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

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  11. Mitophagy Receptors in Tumor Biology.Frontiers in cell and developmental biology · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Hongzhu YanDepartment of Pathology, Seventh People's Hospital of Shanghai University of TCM, Shanghai 200137, P.R. China.
Feng XiaoDepartment of Pathology, Seventh People's Hospital of Shanghai University of TCM, Shanghai 200137, P.R. China.
Jue ZouDepartment of Pathology, Seventh People's Hospital of Shanghai University of TCM, Shanghai 200137, P.R. China.
Chengmin QiuDepartment of Pathology, Songjiang Hospital Affiliated to Τhe First People's Hospital, Shanghai Jiao Tong University, Shanghai 201600, P.R. China.
Weiwei SunDepartment of Pathology, Songjiang Hospital Affiliated to Τhe First People's Hospital, Shanghai Jiao Tong University, Shanghai 201600, P.R. China.
Minmin GuDepartment of Pathology, Songjiang Hospital Affiliated to Τhe First People's Hospital, Shanghai Jiao Tong University, Shanghai 201600, P.R. China.
Li ZhangDepartment of Pathology, Songjiang Hospital Affiliated to Τhe First People's Hospital, Shanghai Jiao Tong University, Shanghai 201600, P.R. China.
Shanghai Jiao Tong University · CNShanghai University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor necrosis factor α (TNFα)-based immunotherapy is the vital host defense system against the progression of gastric cancer (GC) as a pro-inflammatory and pro-apoptotic cytokine. However, resistance limits its therapeutic efficiency. Therefore, an increasing number of studies are focusing on the development of drugs or methods with which to enhance the treatment efficacy of TNFα. Nuclear receptor subfamily 4 group A member 1 (NR4A1) has been shown to exert antitumor effects through several mechanisms, such as by inhibiting proliferation, as well as pro-apoptotic and potent pro-oxidant effects. In this study, we examined the effects and mechanisms of action of NR4A1 on the apoptosis of GC cells treated with TNFα, with particular focus on mitochondrial homeostasis. We found that TNFα treatment decreased NR4A1 expression. Moreover, the overexpression of NR4A1 in the presence of TNFα further increased GC cell apoptosis. Mechanistically, the overexpression of NR4A1 augmented caspase-9-dependent mitochondrial apoptosis, as evidenced by reduced mitochondrial membrane potential, reactive oxygen species (ROS) overproduction, mitochondrial permeability transition pore (mPTP) opening and the leakage of cytochrome c (Cyt-c) leakage. Moreover, NR4A1 overexpression also evoked mitochondrial energy disorder via the suppression of mitochondrial respiratory complex expression. Furthermore, we found that TNFα treatment activated Parkin-dependent mitophagy. Excessive Parkin-dependent mitophagy blocked mitochondrial apoptosis, undermining the toxic effects of TNFα on cells. However, NR4A1 overexpression suppressed Parkin-dependent mitophagy via the inhibition of c-Jun N-terminal kinase (JNK). Re-activation of the JNK/Parkin pathway abrogated the inhibitory effects of NR4A1 on mitophagy, eventually limiting cell apoptosis. Collectively, this study confirmed that NR4A1 sensitizes GC cells to TNFα-induced apoptosis through the inhibition of JNK/Parkin-dependent mitophagy.

Indexed as

ApoptosisCell Line, TumorHumansMAP Kinase Signaling SystemMitophagyNuclear Receptor Subfamily 4, Group A, Member 1Stomach NeoplasmsTumor Necrosis Factor-alphaUbiquitin-Protein LigasesNR4A1 protein, humanNuclear Receptor Subfamily 4, Group A, Member 1parkin proteinTumor Necrosis Factor-alphaUbiquitin-Protein Ligases

Identifiers

PMID29207128
PMCPMC5741370
OpenAlexW2775187110

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.