Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation

Background: In Hong Kong, about 30% of non-small cell lung cancer patients have never smoked tobacco. Among women, 83% are never-smokers and their histological type is invariably adenocarcinoma with 70% incidence of epidermal growth factor receptor (EGFR) mutation. The present study focuses on the microRNA (miRNA) expression profiles of this important subset of lung cancer. Methods: Paired samples collected from the lung cancer tissue and adjacent normal lung parenchyma of 10 non-smoking patients with lung adenocarcinoma were profiled by miRNA microarray. Results were validated by quantitative reverse transcription polymerase chain reaction. Transfected cell viability assays were applied to determine the effects of candidate miRNAs on lung cancer cells. Results: Comparing paired lung cancer tissue with adjacent normal lung parenchyma, hsa-miR-126(center dot), hsa-miR-145, hsa-miR-21, hsa-miR-182, hso-miR-183 and hsa-miR-210 were found to be the most differentially expressed miRNAs. Most interestingly, an obvious inhibition of cell growth was observed in the EGFR mutant lung adenocarcinoma after transfection of hsa-pre-miR-145. Conclusions: Our study is the first report to connect miR-182 to lung cancer. Our results also show that restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in EGFR mutant lung adenocarcinoma. Further study on these specific differentially expressed miRNAs may provide important information on peculiar tumourigenetic pathways and may identify useful biomarkers. (C) 2009 Elsevier Ltd. All rights reserved.