Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation
Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation
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DOI：
10.1016/j.ejca.2009.04.039
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发表时间：
2009-08-01
影响因子：
8.4
通讯作者：
Au, Joseph S. K.
中科院分区：
文献类型：
--
作者：
Cho, William C. S.;Chow, Andrew S. C.;Au, Joseph S. K.
背景：在香港，约30%的非小细胞肺癌患者从未吸烟。在女性中，83%是从不吸烟者，其组织学类型总是腺癌，其中70%发生表皮生长因子受体（EGFR）突变。方法：收集10例非吸烟肺腺癌患者的肺癌组织和癌旁正常肺组织，采用微RNA芯片技术检测其microRNA（miRNA）表达谱。通过定量逆转录聚合酶链反应验证结果。结果：肺癌组织和癌旁正常肺组织中差异表达最高的miRNAs为hsa-miR-126（中点）、hsa-miR-145、hsa-miR-21、hsa-miR-182、hso-miR-183和hsa-miR-210。结论：本研究首次发现miR-182与肺癌的关系。我们的研究结果还表明，肿瘤抑制因子hsa-miR-145的恢复抑制EGFR突变型肺腺癌中的癌细胞生长。对这些特异性差异表达的miRNAs的进一步研究可能为特异性肿瘤发生途径提供重要信息，并可能发现有用的生物标志物。(C)2009爱思唯尔有限公司保留所有权利。
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.