Evidence map›Paper›PMID 31887632›Full record

ArticleTranslational oncology2020

Epigenetic Regulation of RIP3 Suppresses Necroptosis and Increases Resistance to Chemotherapy in NonSmall Cell Lung Cancer.

Qiong Wang, Peipei Wang, Li Zhang, Mathewos Tessema, Lang Bai, Xiuling Xu, Qin Li, Xuelian Zheng, Bryanna Saxton, Wenshu Chen and 7 more

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

Article in Translational oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.1field-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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Multifaceted regulation of immune cells in radiation-induced pulmonary fibrosis: from mechanistic insights to targeted therapies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
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  7. Article
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  9. Article
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  12. Article
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  15. Necroptosis pathways in tumorigenesis.Seminars in cancer biology · 2022
    Review
  16. Review
  17. Article
  18. Article
  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

17 authors at 4 institutions in 2 countries.

Qiong WangMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA; Laboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Peipei WangDepartment of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China.
Li ZhangLaboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Mathewos TessemaMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA.
Lang BaiMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA; Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China.
Xiuling XuMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA.
Qin LiLaboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Xuelian ZhengLaboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Bryanna SaxtonMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA.
Wenshu ChenMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA.
Randy WillinkMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA.
Zhiping LiDepartment of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Lin ZhangLaboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Steven A BelinskyMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA.
Xia WangLaboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: xiawang@scu.edu.cn.
Bin ZhouLaboratory of Molecular and Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China. Electronic address: zhoubin630@scu.edu.cn.
Yong LinMolecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest DR. SE, Albuquerque, NM, 87108, USA. Electronic address: ylin@lrri.org.
Lovelace Respiratory Research Institute · USSichuan University · CNWest China Hospital of Sichuan University · CNWest China Medical Center of Sichuan University · CN

Funding

Targeting RIP3-mediated Necroptosis for ChemosensitizationR21CA193633 · NCI · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · PI LIN, YONG · 2016 to 2017
$515k
NCI NIH HHS R21 CA193633
6 · The paper itself

Abstract

introductionThe efficacy of chemotherapeutic agents in killing cancer cells is mainly attributed to the induction of apoptosis. However, the tremendous efforts on enhancing apoptosis-related mechanisms have only moderately improved lung cancer chemotherapy, suggesting that other cell death mechanisms such as necroptosis could be involved. In this study, we investigated the role of the necroptosis pathway in the responsiveness of nonsmall cell lung cancer (NSCLC) to chemotherapy.

methodsIn vitro cell culture and in vivo xenograft tumor therapy models and clinical sample studies are combined in studying the role of necroptosis in chemotherapy and mechanism of necroptosis suppression involving RIP3 expression regulation.

resultsWhile chemotherapeutic drugs were able to induce necroptotic cell death, this pathway was suppressed in lung cancer cells at least partly through downregulation of RIP3 expression. Ectopic RIP3 expression significantly sensitized lung cancer cells to the cytotoxicity of anticancer drugs such as cisplatin, etoposide, vincristine, and adriamycin. In addition, RIP3 suppression was associated with RIP3 promoter methylation, and demethylation partly restored RIP3 expression and increased chemotherapeutic-induced necroptotic cell death. In a xenograft tumor therapy model, ectopic RIP3 expression significantly sensitized anticancer activity of cisplatin in vivo. Furthermore, lower RIP3 expression was associated with worse chemotherapy response in NSCLC patients.

conclusionOur results indicate that the necroptosis pathway is suppressed in lung cancer through RIP3 promoter methylation, and reactivating this pathway should be exploited for improving lung cancer chemotherapy.

Identifiers

PMID31887632
PMCPMC6938879
OpenAlexW2998690424

What OpenQuestion holds

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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.