Evidence map›Paper›PMID 20964835›Full record

ArticleBMC medicine2010

The VHL-dependent regulation of microRNAs in renal cancer.

Calida S Neal, Michael Z Michael, Lesley H Rawlings, Mark B Van der Hoek, Jonathan M Gleadle

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

Article in BMC medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 7 pooled it
7.0field-weighted citation impact, top 3% 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

84 citing papers in PubMed, 7 syntheses or guidelines pooled it, 161 citations in OpenAlex.

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24 more citing papers are in PubMed but not listed here.

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

5 authors at 4 institutions in 1 country.

Calida S NealRenal Unit, School of Medicine, Flinders University, Flinders Medical Centre, Adelaide, Australia.
Michael Z Michael
Lesley H Rawlings
Mark B Van der Hoek
Jonathan M Gleadle
Flinders Medical Centre · AUCentre for Cancer Biology · AUFlinders University · AUUniversity of Adelaide · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe commonest histological type of renal cancer, clear cell renal cell carcinoma (cc RCC), is associated with genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumour suppressor. VHL inactivation leads to induction of hypoxia-inducible factors (HIFs) and a hypoxic pattern of gene expression. Differential levels of specific microRNAs (miRNAs) are observed in several tumours when compared to normal tissue. Given the central role of VHL in renal cancer formation, we examined the VHL-dependent regulation of miRNAs in renal cancer.

methodsVHL-dependent miRNA expression in cc RCC was determined by microarray analysis of renal cell line RCC4 with mutated VHL (RCC4-VHL) and reintroduced wild-type VHL (RCC4 + VHL). Five miRNAs highly upregulated in RCC4 + VHL and five miRNAs highly downregulated in RCC4 + VHL were studied further, in addition to miR-210, which is regulated by the HIF-VHL system. miRNA expression was also measured in 31 cc RCC tumours compared to adjacent normal tissue.

resultsA significant increase in miR-210, miR-155 and miR-21 expression was observed in the tumour tissue. miR-210 levels also showed a correlation with a HIF-regulated mRNA, carbonic anhydrase IX (CAIX), and with VHL mutation or promoter methylation. An inverse correlation was observed between miR-210 expression and patient survival, and a putative target of miR-210, iron-sulfur cluster assembly protein (ISCU1/2), shows reciprocal levels of mRNA expression in the tumours.

conclusionsWe have identified VHL-regulated miRNAs and found that for some the regulation is HIF-dependent and for others it is HIF-independent. This pattern of regulation was also seen in renal cancer tissue for several of these miRNAs (miR-210, miR-155, let-7i and members of the miR-17-92 cluster) when compared with normal tissue. miR-210 showed marked increases in expression in renal cancer and levels correlated with patient survival. The inverse correlation between miR-210 levels and ISCU1/2 provides support for the hypothesis that ISCU1/2 is a target of miR-210 and that it may contribute to the anaerobic respiration seen in renal (and other) tumours.See Commentary: http://www.biomedcentral.com/1741-7015/8/65.

Indexed as

AdultAgedAged, 80 and overAntigens, NeoplasmBasic Helix-Loop-Helix ProteinsCarbonic Anhydrase IXCarbonic AnhydrasesCarcinoma, Renal CellCell HypoxiaCell Line, TumorEndothelial PAS Domain-Containing Protein 1FemaleGene ExpressionHumansHypoxia-Inducible Factor 1, alpha SubunitIron-Sulfur ProteinsAntigens, NeoplasmBasic Helix-Loop-Helix ProteinsCA9 protein, humanCarbonic Anhydrase IXCarbonic AnhydrasesEndothelial PAS Domain-Containing Protein 1Hypoxia-Inducible Factor 1, alpha SubunitIron-Sulfur ProteinsISCU protein, humanMicroRNAsMIRN155 microRNA, humanMIRN210 microRNA, humanmirnlet7 microRNA, humanVHL protein, humanVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID20964835
PMCPMC2978113
OpenAlexW2131278139

What OpenQuestion holds

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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.