Evidence map›Paper›PMID 29566670›Full record

ArticleBMC cancer2018

The DNA methylation profile of liver tumors in C3H mice and identification of differentially methylated regions involved in the regulation of tumorigenic genes.

Junya Matsushita, Kazuyuki Okamura, Kazuhiko Nakabayashi, Takehiro Suzuki, Yu Horibe, Tomoko Kawai, Toshihiro Sakurai, Satoshi Yamashita, Yoshikazu Higami, Gaku Ichihara and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 20 citations in OpenAlex.

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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 3 institutions in 1 country.

Junya MatsushitaCenter for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Japan.
Kazuyuki OkamuraCenter for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Japan.
Kazuhiko NakabayashiDepartment of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan.
Takehiro SuzukiCenter for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Japan.
Yu HoribeDepartment of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan.
Tomoko KawaiDepartment of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan.
Toshihiro SakuraiGraduate School of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
Satoshi YamashitaNational Cancer Center Japan, Tokyo, Japan.
Yoshikazu HigamiGraduate School of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
Gaku IchiharaGraduate School of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
Kenichiro HataDepartment of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan.
Keiko NoharaCenter for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Japan. keikon@nies.go.jp.ORCID 0000-0001-6529-3316
National Center For Child Health and Development · JPTokyo University of Science · JPNational Institute for Environmental Studies · JP

Funding

Ministry of Education, Culture, Sports, Science and Technology of Japan 15K15246Ministry of Education, Culture, Sports, Science and Technology of Japan 26293154National Institute for Environmental Studies (JP) 1115AA082, 1315AT001, 1620AA041
6 · The paper itself

Abstract

backgroundC3H mice have been frequently used in cancer studies as animal models of spontaneous liver tumors and chemically induced hepatocellular carcinoma (HCC). Epigenetic modifications, including DNA methylation, are among pivotal control mechanisms of gene expression leading to carcinogenesis. Although information on somatic mutations in liver tumors of C3H mice is available, epigenetic aspects are yet to be clarified.

methodsWe performed next generation sequencing-based analysis of DNA methylation and microarray analysis of gene expression to explore genes regulated by DNA methylation in spontaneous liver tumors of C3H mice. Overlaying these data, we selected cancer-related genes whose expressions are inversely correlated with DNA methylation levels in the associated differentially methylated regions (DMRs) located around transcription start sites (TSSs) (promoter DMRs). We further assessed mutuality of the selected genes for expression and DNA methylation in human HCC using the Cancer Genome Atlas (TCGA) database.

resultsWe obtained data on genome-wide DNA methylation profiles in the normal and tumor livers of C3H mice. We identified promoter DMRs of genes which are reported to be related to cancer and whose expressions are inversely correlated with the DNA methylation, including Mst1r, Slpi and Extl1. The association between DNA methylation and gene expression was confirmed using a DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) in Hepa1c1c7 cells and Hepa1-6 cells. Overexpression of Mst1r in Hepa1c1c7 cells illuminated a novel downstream pathway via IL-33 upregulation. Database search indicated that gene expressions of Mst1r and Slpi are upregulated and the TSS upstream regions are hypomethylated also in human HCC. These results suggest that DMRs, including those of Mst1r and Slpi, are involved in liver tumorigenesis in C3H mice, and also possibly in human HCC.

conclusionsOur study clarified genome wide DNA methylation landscape of C3H mice. The data provide useful information for further epigenetic studies of mice models of HCC. The present study particularly proposed novel DNA methylation-regulated pathways for Mst1r and Slpi, which may be applied not only to mouse HCC but also to human HCC.

Indexed as

DNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticAnimalsBinding SitesBiomarkersCarcinoma, HepatocellularCell Line, TumorCell Transformation, NeoplasticCpG IslandsGene Expression ProfilingGenome-Wide Association StudyHumansLiver NeoplasmsMaleMiceBiomarkersTranscription Factors5-aza-2'-deoxycytidineC3H miceDNA methylationLiver tumorsReduced representation bisulfite sequencing (RRBS)

Identifiers

PMID29566670
PMCPMC5865360
OpenAlexW2804444954

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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.