Evidence map›Paper›PMID 27137948›Full record

ArticleMolecular cancer2016

Global, cancer-specific microRNA cluster hypomethylation was functionally associated with the development of non-B non-C hepatocellular carcinoma.

Masanori Nojima, Takeshi Matsui, Akihiro Tamori, Shoji Kubo, Ken Shirabe, Koichi Kimura, Mitsuo Shimada, Tohru Utsunomiya, Yasuteru Kondo, Etsuko Iio and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2016. 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
–field-weighted citation impact
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.

  1. Article
  2. Review
  3. Review
  4. MicroRNA and liver cancer.Cancer drug resistance (Alhambra, Calif.) · 2020
    Review
  5. Article
  6. Article
  7. Epigenetics and MicroRNAs in Cancer.International journal of molecular sciences · 2018
    Review
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.

Masanori NojimaInstitute of Medical Science Hospital, Center for Translational Research, the University of Tokyo, Tokyo, Japan.
Takeshi MatsuiDepartment of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
Akihiro TamoriDepartment of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Shoji KuboDepartment of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Ken ShirabeDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Koichi KimuraDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mitsuo ShimadaDepartment of Surgery, Tokushima University, Tokushima, Japan.
Tohru UtsunomiyaDepartment of Surgery, Tokushima University, Tokushima, Japan.
Yasuteru KondoDivision of Gastroenterology, Tohoku University Hospital, Sendai, Japan.
Etsuko IioDepartment of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Yutaka NaitoDivision of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
Takahiro OchiyaDivision of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
Yasuhito TanakaDepartment of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. ytanaka@med.nagoya-cu.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhile hepatitis B and C viral infection have been suppressed, non-B non-C hepatocellular carcinoma (NBNC-HCC) is considered to be rising in incidence terms in some developed countries where prevalence of those viral infections among HCC patients had been very high (such as Japan, Korea, and Italy). To elucidate critical molecular changes in NBNC-HCC, we integrated three large datasets relating to comprehensive array-based analysis of genome-wide DNA methylation (N = 43 pairs) and mRNA/miRNA expression (N = 15, and 24 pairs, respectively) via statistical modeling.

resultsHierarchical clustering of DNA methylation in miRNA coding regions clearly distinguished NBNC-HCC tissue samples from relevant background tissues, revealing a remarkable tumor-specific hypomethylation cluster. In addition, miRNA clusters were extremely hypomethylated in tumor samples (median methylation change for non-clustered miRNAs: -2.3%, clustered miRNAs: -24.6%). The proportion of CpGs hypomethylated in more than 90% of the samples was 55.9% of all CpGs within miRNA clusters, and the peak methylation level was drastically shifted from 84% to 39%. Following statistical adjustment, the difference in methylation levels within miRNA coding regions was positively associated with their expression change. Receiver operating characteristic (ROC) analysis revealed a great discriminatory ability in respect to cluster-miRNA methylation. Moreover, miRNA methylation change was negatively correlated with corresponding target gene expression amongst conserved and highly matched miRNA sites.

conclusionsWe observed a drastic negative shift of methylation levels in miRNA cluster regions. Changes in methylation status of miRNAs were more indicative of target gene expression and pathological diagnosis than respective miRNA expression changes, suggesting the importance of genome-wide miRNA methylation for tumor development. Our study dynamically summarized global miRNA hypomethylation and its genome-wide scale consequence in NBNC-HCC.

Indexed as

DNA MethylationMultigene FamilyCarcinoma, HepatocellularCell Transformation, NeoplasticCluster AnalysisComputational BiologyEpigenesis, GeneticEpigenomicsGene Expression ProfilingGene Expression Regulation, NeoplasticGenome-Wide Association StudyHumansLiver NeoplasmsMicroRNAsTranscriptomeMicroRNAsGlobal hypomethylationMicroRNAMicroRNA clusterMicroRNA regulationNon-B non-C hepatocellular carcinomaStatistical modeling

Identifiers

PMID27137948
PMCPMC4852433

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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.