MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma

Davidson, MR, Larsen, JE, Yang, IA, Hayward, NK, Clarke, BE, Duhig, EE, Passmore, LH, Bowman, RV and Fong, KM (2010) MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma. PLoS ONE, 5 9: e12560-1-e12560-10. doi:10.1371/journal.pone.0012560

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
Hayward_authaffil_staffdata.pdf Hayward_authaffil_staffdata.pdf application/pdf 181.76KB 0

Author Davidson, MR
Larsen, JE
Yang, IA
Hayward, NK
Clarke, BE
Duhig, EE
Passmore, LH
Bowman, RV
Fong, KM
Title MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2010-09-03
Sub-type Article (original research)
DOI 10.1371/journal.pone.0012560
Open Access Status DOI
Volume 5
Issue 9
Start page e12560-1
End page e12560-10
Total pages 10
Place of publication San Francisco, CA , United States
Publisher Public Library of Science
Collection year 2011
Language eng
Formatted abstract
MicroRNAs (miRNAs) are a family of small, non-coding RNA species functioning as negative regulators of multiple target genes including tumour suppressor genes and oncogenes. Many miRNA gene loci are located within cancer-associated genomic regions. To identify potential new amplified oncogenic and/or deleted tumour suppressing miRNAs in lung cancer, we inferred miRNA gene dosage from high dimensional arrayCGH data. From miRBase v9.0 (http://microrna.sanger.ac.uk), 474 human miRNA genes were physically mapped to regions of chromosomal loss or gain identified from a high-resolution genome-wide arrayCGH study of 132 primary non-small cell lung cancers (NSCLCs) (a training set of 60 squamous cell carcinomas and 72 adenocarcinomas). MiRNAs were selected as candidates if their immediately flanking probes or host gene were deleted or amplified in at least 25% of primary tumours using both Analysis of Copy Errors algorithm and fold change (≥±1.2) analyses. Using these criteria, 97 miRNAs mapped to regions of aberrant copy number. Analysis of three independent published lung cancer arrayCGH datasets confirmed that 22 of these miRNA loci showed directionally concordant copy number variation. MiR-218, encoded on 4p15.31 and 5q35.1 within two host genes (SLIT2 and SLIT3), in a region of copy number loss, was selected as a priority candidate for follow-up as it is reported as underexpressed in lung cancer. We confirmed decreased expression of mature miR-218 and its host genes by qRT-PCR in 39 NSCLCs relative to normal lung tissue. This downregulation of miR-218 was found to be associated with a history of cigarette smoking, but not human papilloma virus. Thus, we show for the first time that putative lung cancer-associated miRNAs can be identified from genome-wide arrayCGH datasets using a bioinformatics mapping approach, and report that miR-218 is a strong candidate tumour suppressing miRNA potentially involved in lung cancer.
© Copyright 2011 Elsevier B.V., All rights reserved.
Keyword Chronic lymphoctic-leukemia
SRC family kinases
Prostate cancer
Chromosmal aberrations
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number e12560.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Publications
Official 2011 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 73 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 84 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 26 Sep 2010, 10:00:58 EST