Evidence map›Paper›PMID 20454457›Full record

ArticlePloS one2010

HOXB13, a target of DNMT3B, is methylated at an upstream CpG island, and functions as a tumor suppressor in primary colorectal tumors.

Kalpana Ghoshal, Tasneem Motiwala, Rainer Claus, Pearlly Yan, Huban Kutay, Jharna Datta, Sarmila Majumder, Shoumei Bai, Arnab Majumder, Tim Huang and 2 more

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
2.8field-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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

  1. A Systematic Review onInternational journal of molecular sciences · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Kalpana GhoshalDepartment of Molecular and Cellular Biochemistry, Ohio State University, Columbus, Ohio, United States of America. kalpana.ghoshal@osumc.edu
Tasneem Motiwala
Rainer Claus
Pearlly Yan
Huban Kutay
Jharna Datta
Sarmila Majumder
Shoumei Bai
Arnab Majumder
Tim Huang
Christoph Plass
Samson T Jacob
The Ohio State University · USGerman Cancer Research Center · DE

Funding

PathologyP01CA101956 · NCI · OHIO STATE UNIVERSITY · PI BYRD, JOHN C. · 2006 to 2010
$11.4M
MOLECULAR MECHANISMS OF DIET-INDUCED CARCINOGENESISR01CA086978 · NCI · OHIO STATE UNIVERSITY · PI GHOSHAL, KALPANA, JACOB, SAMSON T · 2002 to 2018
$4.9M
NCI NIH HHS CA086978NCI NIH HHS CA101956NCI NIH HHS P01 CA101956NCI NIH HHS R01 CA086978
6 · The paper itself

Abstract

backgroundA hallmark of cancer cells is hypermethylation of CpG islands (CGIs), which probably arises from upregulation of one or more DNA methyltransferases. The purpose of this study was to identify the targets of DNMT3B, an essential DNA methyltransferase in mammals, in colon cancer. METHODOLOGY/PRINCIPAL

findingsChromatin immunoprecipitation with DNMT3B specific antibody followed by CGI microarray identified genes with or without CGIs, repeat elements and genomic contigs in RKO cells. ChIP-Chop analysis showed that the majority of the target genes including P16, DCC, DISC1, SLIT1, CAVEOLIN1, GNA11, TBX5, TBX18, HOXB13 and some histone variants, that harbor CGI in their promoters, were methylated in multiple colon cancer cell lines but not in normal colon epithelial cells. Further, these genes were reactivated in RKO cells after treatment with 5-aza-2'-deoxycytidine, a DNA hypomethylating agent. COBRA showed that the CGIs encompassing the promoter and/or coding region of DCC, TBX5, TBX18, SLIT1 were methylated in primary colorectal tumors but not in matching normal colon tissues whereas GNA11 was methylated in both. MassARRAY analysis demonstrated that the CGI located approximately 4.5 kb upstream of HOXB13 +1 site was tumor-specifically hypermethylated in primary colorectal cancers and cancer cell lines. HOXB13 upstream CGI was partially hypomethylated in DNMT1(-/-) HCT cells but was almost methylation free in cells lacking both DNMT1 and DNMT3B. Analysis of tumor suppressor properties of two aberrantly methylated transcription factors, HOXB13 and TBX18, revealed that both inhibited growth and clonogenic survival of colon cancer cells in vitro, but only HOXB13 abolished tumor growth in nude mice. CONCLUSIONS/SIGNIFICANCE: This is the first report that identifies several important tumor suppressors and transcription factors as direct DNMT3B targets in colon cancer and as potential biomarkers for this cancer. Further, this study shows that methylation at an upstream CGI of HOXB13 is unique to colon cancer.

Indexed as

DNA MethylationGene Expression Regulation, NeoplasticGenes, Tumor SuppressorAnimalsBiomarkers, TumorCell Line, TumorColorectal NeoplasmsCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BHomeodomain ProteinsHumansMiceMice, NudeMicroarray AnalysisTranscription FactorsBiomarkers, TumorDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BHomeodomain ProteinsHOXB13 protein, humanTranscription Factors

Identifiers

PMID20454457
PMCPMC2861599
OpenAlexW2102902836

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.