Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
PLoS One. 2010 Feb 15;5(2):e9219. doi: 10.1371/journal.pone.0009219.
MicroRNAs (miRNAs) are small, noncoding RNAs (ribonucleic acids) that regulate translation. Several miRNAs have been shown to be altered in whole cancer tissue compared to normal tissue when quantified by microarray. Based on previous such evidence of differential expression, we chose to study the functional significance of miRNAs miR-30a and -191 alterations in human lung cancer.
METHODOLOGY/PRINCIPAL FINDINGS: The functional significance of miRNAs miR-30a and -191 was studied by creating stable transfectants of the lung adenocarcinoma cell line A549 and the immortalized bronchial epithelial cell line BEAS-2B with modest overexpression of miR-30a or -191 using a lentiviral system. When compared to the corresponding controls, both cell lines overexpressing miR-30a or -191 do not demonstrate any significant changes in cell cycle distribution, cell proliferation, adherent colony formation, soft agar colony formation, xenograft formation in a subcutaneous SCID mouse model, and drug sensitivity to doxorubicin and cisplatin. There is a modest increase in cell migration in cell lines overexpressing miR-30a compared to their controls.
CONCLUSIONS/SIGNIFICANCE: Overexpression of miR-30a or -191 does not lead to an alteration in cell cycle, proliferation, xenograft formation, and chemosensitivity of A549 and BEAS-2B cell lines. Using microarray data from whole tumors to select specific miRNAs for functional study may be a suboptimal strategy.
microRNAs(miRNAs)是一种小的非编码 RNA(核糖核酸),可以调节翻译。通过微阵列定量分析,已经证明在整个肿瘤组织中,与正常组织相比,有几种 miRNA 发生了改变。基于先前关于差异表达的证据,我们选择研究人肺癌中 miRNA miR-30a 和 -191 改变的功能意义。
方法/主要发现:通过使用慢病毒系统对肺腺癌细胞系 A549 和永生化的支气管上皮细胞系 BEAS-2B 进行适度过表达 miR-30a 或 -191 的稳定转染,研究了 miRNA miR-30a 和 -191 的功能意义。与相应的对照相比,过表达 miR-30a 或 -191 的两种细胞系在细胞周期分布、细胞增殖、贴壁集落形成、软琼脂集落形成、SCID 皮下异种移植形成以及对阿霉素和顺铂的药物敏感性方面均未显示出任何显著变化。与对照相比,过表达 miR-30a 的细胞系中的细胞迁移略有增加。
结论/意义:过表达 miR-30a 或 -191 不会导致 A549 和 BEAS-2B 细胞系的细胞周期、增殖、异种移植形成和化疗敏感性发生改变。使用来自整个肿瘤的微阵列数据来选择特定的 miRNA 进行功能研究可能不是一种最佳策略。