Evidence map›Paper›PMID 34645486›Full record

ArticleJournal of experimental & clinical cancer research : CR2021

An SETD1A/Wnt/β-catenin feedback loop promotes NSCLC development.

Rui Wang, Jian Liu, Kai Li, Ganghua Yang, Sisi Chen, Jie Wu, Xinming Xie, Hong Ren, Yamei Pang

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

40 citing papers in PubMed, 51 citations in OpenAlex.

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  17. Transcriptomic Changes in Cisplatin-Resistant MCF-7 Cells.International journal of molecular sciences · 2024
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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 1 institution in 1 country.

Rui Wang *Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, P.R. China.
Jian Liu *Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, P.R. China.
Kai Li *Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, P.R. China.
Ganghua YangDepartment of Geriatric Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.
Sisi ChenDepartment of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, P.R. China.
Jie WuDepartment of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, P.R. China.
Xinming XieDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 277 Yanta West Road, Xi'an, 710061, Shaanxi Province, China.
Hong RenDepartment of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, P.R. China. renh_med@163.com.
Yamei PangDepartment of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 277 Yanta West Road, Xi'an, 710061, Shaanxi Province, China. dr_pangym@163.com.
First Affiliated Hospital of Xi'an Jiaotong University · CN

Funding

National Natural Science Foundation of China 81272418Scientific and Technological Development Research Project Foundation of Shaanxi Province 2020SF-069Young Scientists Fund 81800052Young Scientists Fund 81903040
6 · The paper itself

Abstract

backgroundSETD1A, a member of SET1/MLL family H3K4 methyltransferases, is involved in the tumorigenesis of numerous cancers. However, the biological role and mechanism of SETD1A in non-small cell lung cancer (NSCLC) remain to be elucidated.

methodsThe expression of SETD1A, NEAT1, EZH2, and β-catenin in NSCLC tissues and cell lines was detected by qRT-PCR, immunohistochemistry and western blotting. The regulatory mechanisms were validated by chromatin immunoprecipitation, co-immunoprepitation and luciferase reporter assay. The self-renewal, cisplatin sensitivity and tumorigenesis of NSCLC cells were analyzed using sphere formation, CCK-8, colony formation assays and xenograft tumor models.

resultsSETD1A expression was significantly increased in NSCLC and its overexpression predicted a poor prognosis of patients with NSCLC. Functional experiments showed that SETD1A positively regulated cancer stem cell property and negatively regulated cisplatin sensitivity in NSCLC cells via the Wnt/β-catenin pathway. Next, we found that SETD1A positively regulated the Wnt/β-catenin pathway via interacting with and stabilizing β-catenin. The SET domain is dispensable for the interaction between SETD1A and β-catenin. Furthermore, we identified that SETD1A bound to the promoters of NEAT1 and EZH2 to activate gene transcription by inducing H3K4me3 enrichment. Rescue experiments showed that SETD1A promoted the Wnt/β-catenin pathway and exerted its oncogenic functions in NSCLC, at least, partly through NEAT1 and EZH2 upregulation. In addition, SETD1A was proven to be a direct target of the Wnt/β-catenin pathway, thus forming a positive feedback loop in NSCLC cells.

conclusionSETD1A and Wnt/β-catenin pathway form a positive feedback loop and coordinately contribute to NSCLC progression.

Indexed as

Animalsbeta CateninCarcinoma, Non-Small-Cell LungFeedbackFemaleHistone-Lysine N-MethyltransferaseHumansLung NeoplasmsMiceTransfectionWnt Signaling Pathwaybeta CateninHistone-Lysine N-MethyltransferaseNsccn1 protein, mouseEZH2NEAT1NSCLCSETD1Aβ-Catenin

Identifiers

PMID34645486
PMCPMC8513302
OpenAlexW3206224688

What OpenQuestion holds

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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.