Evidence map›Paper›PMID 27212034›Full record

ArticleOncogene2017

REC8 functions as a tumor suppressor and is epigenetically downregulated in gastric cancer, especially in EBV-positive subtype.

J Yu, Q Liang, J Wang, K Wang, J Gao, J Zhang, Y Zeng, P W Y Chiu, E K W Ng, J J Y Sung

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

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 59 citations in OpenAlex.

  1. Genes & diseases · 2026
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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

10 authors at 3 institutions in 1 country.

J YuInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
Q LiangInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
J WangInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
K WangInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
J GaoDepartment of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
J ZhangInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
Y ZengInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
P W Y ChiuDepartment of Surgery, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
E K W NgDepartment of Surgery, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
J J Y SungInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
Chinese University of Hong Kong, Shenzhen · CNChinese University of Hong Kong · CNPeking University Cancer Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

REC8 meiotic recombination protein (REC8) was found to be preferentially methylated in gastric cancer (GC) using promoter methylation array. We aimed to elucidate the epigenetic alteration and biological function of REC8 in GC. REC8 was downregulated in 100% (3/3) of Epstein-Barr virus (EBV)-positive and 80% (8/10) of EBV-negative GC cell lines by promoter methylation, but the expression could be restored through demethylation treatment. Protein expression of REC8 was significantly lower in human primary gastric tumors than in adjacent non-tumor tissues. A negative correlation between methylation and mRNA expression of REC8 was observed in 223 gastric samples of The Cancer Genome Atlas study (r=-0.7018, P<0.001). The methylation level (%) of the REC8 promoter was significantly higher in EBV-positive gastric tumors than in EBV-negative gastric tumors, as shown by bisulfite genomic sequencing (77.6 (69.3-80.5) vs 51.4 (39.5-62.3), median (interquartile range); P<0.001); methylation levels in both subtypes of tumors were significantly higher than in normal stomach tissues (14.8 (4.2-24.0)) (both P<0.001). Multivariate analysis revealed that REC8 methylation was an independent factor for poor survival in GC patients (hazard ratio=1.68, P<0.05). REC8 expression significantly suppressed cell viability, clonogenicity and cell cycle progression; it induced apoptosis and inhibited migration of AGS-EBV (EBV-positive) and BGC823 (EBV-negative) GC cells, and it suppressed tumorigenicity in nude mice. In contrast, knockdown of REC8 in gastric epithelial immortalized GES-1 cells significantly increased cell viability, clonogenicity and migration ability. The tumor-suppressive effect of REC8 is mediated at least in part by the downregulation of genes involved in cell growth (G6PD, SLC2A1, NOL3, MCM2, SNAI1 and SNAI2), and the upregulation of apoptosis/migration inhibitors (GADD45G and LDHA) and tumor suppressors (PinX1, IGFBP3 and ETS2). In conclusion, REC8 is a novel tumor suppressor that is commonly downregulated by promoter methylation in GC, especially in the EBV-associated subtype. Promoter methylation of REC8 is an independent risk factor for the shortened survival of GC patients.

Indexed as

DNA MethylationDown-RegulationAdultAgedAnimalsCell Cycle ProteinsCell Line, TumorCell MovementEpigenesis, GeneticEpstein-Barr Virus InfectionsFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, NudeCell Cycle ProteinsREC8 protein, human

Identifiers

PMID27212034
PMCPMC5241426
OpenAlexW2400122764

What OpenQuestion holds

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LicenceCC BY-NC-SA
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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.