Evidence map›Paper›PMID 25860510›Full record

ArticlePloS one2015

The role of HOXB9 and miR-196a in head and neck squamous cell carcinoma.

Lav Darda, Fahad Hakami, Richard Morgan, Craig Murdoch, Daniel W Lambert, Keith D Hunter

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. 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
3.0field-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

37 citing papers in PubMed, 59 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

6 authors at 2 institutions in 2 countries.

Lav DardaUnit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Fahad HakamiUnit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Richard MorganInstitute of Cancer Therapeutics, University of Bradford, Bradford, United Kingdom.
Craig MurdochUnit of Oral and Maxillofacial Medicine & Surgery, School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Daniel W LambertUnit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom.
Keith D HunterUnit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, United Kingdom; Department of Oral Pathology and Biology, University of Pretoria, Pretoria, South Africa.
University of Sheffield · GBUniversity of Bradford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrevious studies have demonstrated that a number of HOX genes, a family of transcription factors with key roles in early development, are up-regulated in head and neck squamous cell carcinoma (HNSCC) and other cancers. The loci of several Homeobox (HOX) genes also contain microRNAs (miRs), including miR-196a.

methodsGlobal miR expression and expression of all 39 HOX genes in normal oral keratinocytes (NOKs), oral pre-malignant (OPM) and HNSCC cells was assessed by expression microarray and qPCR and in tissues by immunohistochemistry (IHC) and qPCR of laser microdissected (LCM) tissues. Expression of miR196a and HOXB9 was reduced using anti-miR-196a and siRNA, respectively. Expression microarray profiles of anti-miR196a and pre-miR196a transfected cells were compared to parental cells in order to identify novel targets of miR-196a. Putative miR196a targets were validated by qPCR and were confirmed as binding to the 3'UTR of miR196a by a dual luciferase reporter assay combined with mutational analysis of the miR-196a binding site.

resultsmiR-196a and HOXB9 are highly expressed in HNSCC compared to NOKs, a pattern also seen in HNSCC tissues by HOXB9 IHC and qPCR of miR-196a in LCM tissue. Knock-down of miR-196a expression decreased HNSCC cell migration, invasion and adhesion to fibronectin, but had no effect on proliferation. Furthermore, knock-down of HOXB9 expression decreased migration, invasion and proliferation but did not alter adhesion. We identified a novel primary mRNA transcript containing HOXB9 and miR196a-1 as predicted from in-silico analysis. Expression array analysis identified a number of miR196a targets, including MAMDC2 and HOXC8. We confirmed that MAMDC2 is a novel miR-196a target using a dual luciferase reporter assay with the effect abolished on mutation of the binding site.

conclusionsThese results show that miR-196a and HOXB9 are overexpressed, perhaps co-ordinately, as HNSCC develops and exert a pro-tumourigenic phenotype in HNSCC and OPM cells.

Indexed as

3' Untranslated RegionsBinding SitesCarcinoma, Squamous CellCell AdhesionCell Line, TumorCell MovementCell ProliferationFibronectinsGPI-Linked ProteinsHead and Neck NeoplasmsHomeodomain ProteinsHumansImmunohistochemistryMicroRNAsMouth MucosaNeural Cell Adhesion Molecules3' Untranslated RegionsFibronectinsGPI-Linked ProteinsHomeodomain ProteinsHOXB9 protein, humanMDGA2 protein, humanMicroRNAsMIRN196 microRNA, humanNeural Cell Adhesion MoleculesOligonucleotides, AntisenseRNA, Small Interfering

Identifiers

PMID25860510
PMCPMC4393232
OpenAlexW2068378646

What OpenQuestion holds

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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.