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Unformatted text preview: ORIGINAL PAPER The let-7a microRNA protects from growth of lung carcinoma by suppression of k-Ras and c-Myc in nude mice Xiao-yan He Jun-xia Chen Zheng Zhang Chun-lei Li Qiong-le Peng Hui-min Peng Received: 23 September 2009 / Accepted: 7 December 2009 Springer-Verlag 2009 Abstract Purpose Down-regulation of let-7 microRNA (miRNA) plays an important role in the pathogenesis of lung cancer. k-Ras and c-Myc, two key oncogenes in lung cancer, have been found to be targeted by let-7 in vitro. However, the in vivo relevance of these findings is unknown. The aim of the present study is to determine the effect of let-7a, a member of let-7 family, on the growth of lung cancer in vivo and to investigate whether let-7-induced suppression of k-Ras and c-Myc is involved in lung cancer. Methods A549-let-7a cell line and A549-control cell line, two stable transfected cell lines over-expressing let-7a and the control miRNA, were established and preserved in our lab. A549, A549-control, and A549-let-7a cells were injected subcutaneously into nude mice, respectively. After 30 days, the mice were killed; the xenografts were excised and weighed. The expression of let-7a in tumor xenografts was assessed by real-time reverse transcription-PCR (RT- PCR). The expression of k-Ras and c-Myc in xenografts were determined by western blot and immunohistochem- istry detection. Results Real-time RT-PCR showed the expression of let- 7a was increased significantly in A549-let-7a cells-injected group, compared with A549-control cells-injected group and A549 cells-injected group ( P \ 0.01). In the xeno- grafts of A549-let-7a cells-injected group, a significant depression in tumor weight ( P \ 0.05) and significant decrease of k-Ras and c-Myc protein were observed ( P \ 0.01), compared to A549 cells-injected group and A549-control cells-injected group. Conclusion Overexpression of let-7a can inhibit the growth of lung cancer transplanted subcutaneously in nude mice by suppression of k-Ras and c-Myc. Keywords Let-7a MicroRNA Lung cancer Nude mice Tumor treatment Introduction Lung cancer is the most common cause of cancer deaths around the world. Its incidence continues to increase at a rate of approximately 0.5% per year, and the number of cancer deaths caused by this disease expected to rise to 50% by 2020 (Jemal et al. 2008 ). Despite recent progress in diagnosis and multimodality therapies for lung cancer, the prognosis still remain unsatisfactory with 5-year survival rates of less than 15%. They highlight the fact that new strategies based on molecular mechanisms are required for lung cancer treatment. Although several genetic or epige- netic changes in critical genes have been implicated to lung cancer, the mechanism relevant to lung carcinogenesis is not fully understood....
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