Evidence map›Paper›PMID 24516043›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014

Reduced expression of miRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11.

Ross M Drayton, Ewa Dudziec, Stefan Peter, Simone Bertz, Arndt Hartmann, Helen E Bryant, James Wf Catto

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

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 3 pooled it
6.5field-weighted citation impact, top 2% 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

134 citing papers in PubMed, 3 syntheses or guidelines pooled it, 223 citations in OpenAlex.

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  20. Disulfidptosis: A new type of cell death.Apoptosis : an international journal on programmed cell death · 2024
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74 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

7 authors at 2 institutions in 2 countries.

Ross M DraytonAuthors' Affiliations: Academic Unit of Molecular Oncology and Academic Urology Unit, University of Sheffield, Sheffield, United Kingdom; Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom; and Department of Pathology, University of Erlangen, Germany.
Ewa Dudziec
Stefan Peter
Simone Bertz
Arndt Hartmann
Helen E Bryant
James Wf Catto
University of Oxford · GBUniversity of Sheffield · GB

Funding

Yorkshire Cancer Research S310
6 · The paper itself

Abstract

purposeResistance to cisplatin-based chemotherapy is a major obstacle to bladder cancer treatment. We aimed to identify microRNAs (miRNA) that are dysregulated in cisplatin-resistant disease, ascertain how these contribute to a drug-resistant phenotype, and how this resistance might be overcome. EXPERIMENTAL

designmiRNA expression in paired cisplatin-resistant and -sensitive cell lines was measured. Dysregulated miRNAs were further studied for their ability to mediate resistance. The nature of the cisplatin-resistant phenotype was established by measurement of cisplatin/DNA adducts and intracellular glutathione (GSH). Candidate miRNAs were examined for their ability to (i) mediate resistance and (ii) alter the expression of a candidate target protein (SLC7A11); direct regulation of SLC7A11 was confirmed using a luciferase assay. SLC7A11 protein and mRNA, and miRNA-27a were quantified in patient tumor material.

resultsA panel of miRNAs were found to be dysregulated in cisplatin-resistant cells. miRNA-27a was found to target the cystine/glutamate exchanger SLC7A11 and to contribute to cisplatin resistance through modulation of GSH biosynthesis. In patients, SLC7A11 expression was inversely related to miRNA-27a expression, and those tumors with high mRNA expression or high membrane staining for SLC7A11 experienced poorer clinical outcomes. Resistant cell lines were resensitized by restoring miRNA-27a expression or reducing SLC7A11 activity with siRNA or with sulfasalazine.

conclusionOur findings indicate that miRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy. SLC7A11 inhibition with sulfasalazine may be a promising therapeutic approach to the treatment of cisplatin-resistant disease.

Indexed as

AgedAged, 80 and overAmino Acid Transport System y+Cell Line, TumorCisplatinDNA AdductsDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansMaleMicroRNAsMiddle AgedRandomized Controlled Trials as TopicUrinary Bladder NeoplasmsAmino Acid Transport System y+Cisplatincisplatin-DNA adductDNA AdductsMicroRNAsMIRN27 microRNA, humanSLC7A11 protein, human

Identifiers

PMID24516043
PMCPMC3974662
OpenAlexW2155781648

What OpenQuestion holds

Textmetadata
LicenceTDM
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.