PMID- 22282464
OWN - NLM
STAT- MEDLINE
DCOM- 20120628
LR  - 20220317
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 18
IP  - 6
DP  - 2012 Mar 15
TI  - Genome-wide miRNA expression profiling identifies miR-9-3 and miR-193a as targets 
      for DNA methylation in non-small cell lung cancers.
PG  - 1619-29
LID - 10.1158/1078-0432.CCR-11-2450 [doi]
AB  - 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.
FAU - Heller, Gerwin
AU  - Heller G
AD  - Department of Medicine I, Medical University of Vienna, Vienna, Austria.
FAU - Weinzierl, Marlene
AU  - Weinzierl M
FAU - Noll, Christian
AU  - Noll C
FAU - Babinsky, Valerie
AU  - Babinsky V
FAU - Ziegler, Barbara
AU  - Ziegler B
FAU - Altenberger, Corinna
AU  - Altenberger C
FAU - Minichsdorfer, Christoph
AU  - Minichsdorfer C
FAU - Lang, Gyorgy
AU  - Lang G
FAU - Dome, Balazs
AU  - Dome B
FAU - End-Pfutzenreuter, Adelheid
AU  - End-Pfutzenreuter A
FAU - Arns, Britt-Madeleine
AU  - Arns BM
FAU - Grin, Yuliya
AU  - Grin Y
FAU - Klepetko, Walter
AU  - Klepetko W
FAU - Zielinski, Christoph C
AU  - Zielinski CC
FAU - Zochbauer-Muller, Sabine
AU  - Zochbauer-Muller S
LA  - eng
GR  - P 24130/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120126
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (MIRN193 microRNA, human)
RN  - 0 (MIRN92 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 776B62CQ27 (Decitabine)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Azacitidine/analogs & derivatives/pharmacology
MH  - Carcinoma, Non-Small-Cell Lung/*genetics
MH  - Cell Line, Tumor
MH  - *DNA Methylation
MH  - Decitabine
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Silencing
MH  - Humans
MH  - Hydroxamic Acids/pharmacology
MH  - Lung/metabolism
MH  - Lung Neoplasms/*genetics
MH  - Male
MH  - MicroRNAs/*metabolism
MH  - Middle Aged
MH  - Molecular Targeted Therapy
MH  - Oligonucleotide Array Sequence Analysis
EDAT- 2012/01/28 06:00
MHDA- 2012/06/29 06:00
CRDT- 2012/01/28 06:00
PHST- 2012/01/28 06:00 [entrez]
PHST- 2012/01/28 06:00 [pubmed]
PHST- 2012/06/29 06:00 [medline]
AID - 1078-0432.CCR-11-2450 [pii]
AID - 10.1158/1078-0432.CCR-11-2450 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2012 Mar 15;18(6):1619-29. doi: 10.1158/1078-0432.CCR-11-2450. 
      Epub 2012 Jan 26.