RGD Reference Report - Genome-wide miRNA expression profiling identifies miR-9-3 and miR-193a as targets for DNA methylation in non-small cell lung cancers. - Rat Genome Database

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Genome-wide miRNA expression profiling identifies miR-9-3 and miR-193a as targets for DNA methylation in non-small cell lung cancers.

Authors: Heller, Gerwin  Weinzierl, Marlene  Noll, Christian  Babinsky, Valerie  Ziegler, Barbara  Altenberger, Corinna  Minichsdorfer, Christoph  Lang, György  Döme, Balazs  End-Pfützenreuter, Adelheid  Arns, Britt-Madeleine  Grin, Yuliya  Klepetko, Walter  Zielinski, Christoph C  Zöchbauer-Müller, Sabine 
Citation: Heller G, etal., Clin Cancer Res. 2012 Mar 15;18(6):1619-29. doi: 10.1158/1078-0432.CCR-11-2450. Epub 2012 Jan 26.
RGD ID: 153344598
Pubmed: PMID:22282464   (View Abstract at PubMed)
DOI: DOI:10.1158/1078-0432.CCR-11-2450   (Journal Full-text)


PURPOSE: The major aim of this study was to investigate the role of DNA methylation (referred to as methylation) on miRNA silencing in non-small cell lung cancers (NSCLC).
EXPERIMENTAL DESIGN: We conducted microarray expression analyses of 856 miRNAs in NSCLC A549 cells before and after treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (Aza-dC) and with a combination of Aza-dC and the histone deacetylase inhibitor trichostatin A. miRNA methylation was determined in 11 NSCLC cell lines and in primary tumors and corresponding nonmalignant lung tissue samples of 101 patients with stage I-III NSCLC.
RESULTS: By comparing microarray data of untreated and drug-treated A549 cells, we identified 33 miRNAs whose expression was upregulated after drug treatment and which are associated with a CpG island. Thirty (91%) of these miRNAs were found to be methylated in at least 1 of 11 NSCLC cell lines analyzed. Moreover, miR-9-3 and miR-193a were found to be tumor specifically methylated in patients with NSCLC. We observed a shorter disease-free survival of patients with miR-9-3 methylated lung squamous cell carcinoma (LSCC) than patients with miR-9-3 unmethylated LSCC by multivariate analysis [HR = 3.8; 95% confidence interval (CI), 1.3-11.2, P = 0.017] and a shorter overall survival of patients with miR-9-3 methylated LSCC than patients with miR-9-3 unmethylated LSCC by univariate analysis (P = 0.013).
CONCLUSIONS: Overall, our results suggest that methylation is an important mechanism for inactivation of certain miRNAs in NSCLCs and that miR-9-3 methylation may serve as a prognostic parameter in patients with LSCC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung squamous cell carcinoma exacerbatesIDA 153344598; 153344598DNA:HypermethylationRGD 
lung squamous cell carcinoma exacerbatesISOMIR193A (Homo sapiens)153344598; 153344598DNA:HypermethylationRGD 
lung squamous cell carcinoma exacerbatesISOMIR9-3 (Homo sapiens)153344598; 153344598DNA:HypermethylationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir193a  (microRNA 193a)
Mir9-3  (microRNA 9-3)

Genes (Mus musculus)
Mir193a  (microRNA 193a)
Mir9-3  (microRNA 9-3)

Genes (Homo sapiens)
MIR193A  (microRNA 193a)
MIR9-3  (microRNA 9-3)


Additional Information