Evidence map›Paper›PMID 30348169›Full record

ArticleMolecular cancer2018

Targeting histone methyltransferase G9a inhibits growth and Wnt signaling pathway by epigenetically regulating HP1α and APC2 gene expression in non-small cell lung cancer.

Keqiang Zhang, Jinhui Wang, Lu Yang, Yate-Ching Yuan, Tommy R Tong, Jun Wu, Xinwei Yun, Melissa Bonner, Rajendra Pangeni, Zheng Liu and 3 more

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

51 citing papers in PubMed, 94 citations in OpenAlex.

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  7. EHMT2-mediated transcriptional reprogramming drives neuroendocrine transformation in non-small cell lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 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

13 authors at 1 institution in 1 country.

Keqiang ZhangDivision of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA. kzhang@coh.org.ORCID 0000-0002-4210-4401
Jinhui WangThe Integrative Genomics Core lab of Department of Molecular Medicine, City of Hope National Medical Center, Duarte, CA, USA.
Lu YangThe Integrative Genomics Core lab of Department of Molecular Medicine, City of Hope National Medical Center, Duarte, CA, USA.
Yate-Ching YuanThe Bioinformatics Core lab of Department of Molecular Medicine, City of Hope Medical Center, Duarte, CA, USA.
Tommy R TongDepartment of Pathology, City of Hope Medical Center, Duarte, CA, USA.
Jun WuDivision of Comparative Medicine, City of Hope National Medical Center, Duarte, CA, USA.
Xinwei YunDivision of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA.
Melissa BonnerDivision of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA.
Rajendra PangeniDivision of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA.
Zheng LiuThe Bioinformatics Core lab of Department of Molecular Medicine, City of Hope Medical Center, Duarte, CA, USA.
Tiger YuchiDivision of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA.
Jae Y KimDivision of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA.
Dan J RazDivision of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA. draz@coh.org.
City Of Hope National Medical Center · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Oncology Research Career Development ProgramK12CA001727 · NCI · CITY OF HOPE NATIONAL MEDICAL CENTER · PI MORTIMER, JOANNE E. · 1992 to 2024
$14.6M
NCI NIH HHS K12 CA001727NCI NIH HHS P30 CA033572
6 · The paper itself

Abstract

backgroundDysregulated histone methyltransferase G9a may represent a potential cancer therapeutic target. The roles of G9a in tumorigenesis and therapeutics are not well understood in non-small cell lung cancer (NSCLC). Here we investigated the impact of G9a on tumor growth and signaling pathways in NSCLC.

methodsImmunohistochemistry analyzed G9a expression in NSCLC tissues. Both siRNA and selective inhibitor were used to target G9a. The impact of targeting G9a on key genes, signaling pathways and growth were investigated in NSCLC cells by RNA sequencing analysis, rescue experiments, and xenograft models.

resultsOverexpression of G9a (≥ 5% of cancer cells showing positive staining) was found in 43.2% of 213 NSCLC tissues. Multiple tumor-associated genes including HP1α, APC2 are differentially expressed; and signaling pathways involved in cellular growth, adhesion, angiogenesis, hypoxia, apoptosis, and canonical Wnt signaling pathways are significantly altered in A549, H1299, and H1975 cells upon G9a knockdown. Additionally, targeting G9a by siRNA-mediated knockdown or by a selective G9a inhibitor UNC0638 significantly inhibited tumor growth, and dramatically suppressed Wnt signaling pathway in vitro and in vivo. Furthermore, we showed that treatment with UNC0638 restores the expression of APC2 expression in these cells through promoter demethylation. Restoring HP1α and silencing APC2 respectively attenuated the inhibitory effects on cell proliferation and Wnt signaling pathway in cancer cells in which G9a was silenced or suppressed.

conclusionsThese findings demonstrate that overexpressed G9a represents a promising therapeutic target, and targeting G9a potentially suppresses growth and Wnt signaling pathway partially through down-regulating HP1α and epigenetically restoring these tumor suppressors such as APC2 that are silenced in NSCLC.

Indexed as

Gene Expression Regulation, NeoplasticWnt Signaling PathwayAnimalsApoptosisCarcinoma, Non-Small-Cell LungCell Cycle CheckpointsCell Line, TumorCell MovementCell ProliferationChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneCytoskeletal ProteinsDisease Models, AnimalDNA MethylationEpigenesis, GeneticGene Expression ProfilingAPC2 protein, humanCBX5 protein, humanChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneCytoskeletal ProteinsEHMT2 protein, humanHistocompatibility AntigensHistone-Lysine N-MethyltransferaseQuinazolinesUNC 0638APC2Cell growthHP1αNSCLC, histone methyltransferase G9aWnt signaling pathway

Identifiers

PMID30348169
PMCPMC6198520
OpenAlexW2895790180

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.