Department of Geriatrics, The Affiliated Zhongshan Hospital of Fudan University, Shanghai, China.
Cancer Biother Radiopharm. 2013 Mar;28(2):131-7. doi: 10.1089/cbr.2012.1307. Epub 2012 Nov 7.
MicroRNAs are closely linked to tumor metastasis and let-7a may play a role in inhibiting the proliferation, invasion, and metastasis of lung cancer. In vitro, we aim to observe the impact of let-7a on the proliferation and invasion of the nonsmall cell lung cancer cell line 95D by constructing a lentiviral vector that expresses let-7a. Cell proliferation assays and Transwell experiments were used to compare the proliferation and invasion of the 95D cell group with let-7a overexpressed or inhibited. Real-time polymerase chain reaction and immunoblotting analysis were used to compare the expression of K-RAS and HMGA2 at mRNA and the protein level in the above groups. The results showed the cells in the let-7a overexpressed group were significantly less proliferative and invasive than those in the let-7a inhibited group (p < 0.05). K-RAS and HMGA2 mRNA levels were significantly higher in the let-7a overexpressed group than those in the let-7a inhibited group (p < 0.05). However, the protein levels of K-RAS and HMGA2 were significantly lower in the let-7a overexpressed group than those in the let-7a inhibited group (p < 0.05). We suppose that let-7a inhibits the proliferation and invasion of the cell line 95D by regulating the translation of K-RAS and HMGA2 mRNA, not the transcription of the mRNA itself.
微小 RNA 与肿瘤转移密切相关,let-7a 可能在抑制肺癌的增殖、侵袭和转移中发挥作用。在体外,我们旨在通过构建表达 let-7a 的慢病毒载体,观察 let-7a 对非小细胞肺癌细胞系 95D 增殖和侵袭的影响。通过细胞增殖试验和 Transwell 实验,比较 let-7a 过表达或抑制组 95D 细胞的增殖和侵袭能力。实时聚合酶链反应和免疫印迹分析用于比较上述各组中 K-RAS 和 HMGA2 在 mRNA 和蛋白水平上的表达。结果显示,let-7a 过表达组细胞的增殖和侵袭能力明显低于 let-7a 抑制组(p<0.05)。let-7a 过表达组 K-RAS 和 HMGA2 mRNA 水平明显高于 let-7a 抑制组(p<0.05)。然而,let-7a 过表达组 K-RAS 和 HMGA2 的蛋白水平明显低于 let-7a 抑制组(p<0.05)。我们推测,let-7a 通过调节 K-RAS 和 HMGA2 mRNA 的翻译而不是 mRNA 本身的转录来抑制细胞系 95D 的增殖和侵袭。