Evidence map›Paper›PMID 27223069›Full record

ArticleOncotarget2016

Higher methylation intensity induced by EBV LMP1 via NF-κB/DNMT3b signaling contributes to silencing of PTEN gene.

Hong Peng, Yuxiang Chen, Pinggui Gong, Longmei Cai, Xiaoming Lyu, Qiang Jiang, Jianguo Wang, Juan Lu, Kaitai Yao, Kunping Liu and 2 more

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.2field-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

37 citing papers in PubMed, 44 citations in OpenAlex.

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  18. Role of Virus-Induced Host Cell Epigenetic Changes in Cancer.International journal of molecular sciences · 2021
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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

12 authors at 4 institutions in 1 country.

Hong PengDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Yuxiang ChenDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Pinggui GongDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Longmei CaiDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Xiaoming LyuDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Qiang JiangDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Jianguo WangDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Juan LuDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Kaitai YaoDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Kunping LiuDepartment of Pathology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, China.
Jinbang LiDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Xin LiDepartment of Otorhinolaryngology at Nanfang Hospital, Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
Nanfang Hospital · CNSouthern Medical University · CNGuangdong Provincial People's Hospital · CNGuangzhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phosphatase and tensin homolog (PTEN) is a major tumor suppressor and usually silenced via the deletion, insertion and mutation. We previously discovered its inactivation via aberrant CpG island methylation. Here, we provide further evidence that EBV latent membrane protein 1(LMP1) can induce a higher intensity of DNA methylation at PTEN CpG islands, inactivating PTEN at the cellular and molecular level. Initially, increased methylation intensity of PTEN CpG islands was observed in EBV-infected nasopharyngeal carcinoma (NPC) cells, accompanied by decreased PTEN expression. In NPC tissue samples showing the methylation at PTEN promoter, LMP1 was highly expressed in higher methylation intensity group relative to lower intensity group, and DNA methyltransferase 3b (DNMT3b) expression was positively correlated with LMP1 expression. Moreover, transfection of LMP1 gene into EBV-negative NPC cells demonstrated that LMP1 up-regulated DNMT3b expression, leading to a higher intensity of PTEN CpG island methylation. Mechanistically, computational prediction and luciferase reporter assay identified a functional NF-κB binding site on DNMT3b promoter and the mutated NF-κB binding site abolished LMP1-mediated DNMT3b activation. Chromatin immunoprecipitation displayed that NF-κB p65 subunit constitutively bound to DNMT3b promoter, supporting the activation of DNMT3b by EBV LMP1 via NF-κB signaling. Furthermore, the expression level of DNMT3b was observed to be increased in the nuclei of LMP1-expressing NPC cells, and a NF-κB inhibitor, PDTC, counteracted LMP1-mediated DNMT3b overexpression. Thus, this study first reports that LMP1-mediated NF-κB can up-regulate DNMT3b transcription, thereby leading to relatively higher methylation intensity at PTEN CpG islands, and ultimately silencing major tumor suppressor PTEN.

Indexed as

CpG IslandsDNA MethylationAgedCarcinomaCell NucleusDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BFemaleGene SilencingHEK293 CellsHerpesvirus 4, HumanHumansMaleMiddle AgedNasopharyngeal CarcinomaNasopharyngeal NeoplasmsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BEBV-associated membrane antigen, Epstein-Barr virusNF-kappa BPTEN PhosphohydrolasePTEN protein, humanViral Matrix ProteinsDNA methylationDNMT3bEBVLMP1PTEN

Identifiers

PMID27223069
PMCPMC5129989
OpenAlexW2402202451

What OpenQuestion holds

Textmetadata
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.