let-7a_cell_bio - ORIGINAL PAPER The let-7a microRNA...

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

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....
View Full Document

Page1 / 6

let-7a_cell_bio - ORIGINAL PAPER The let-7a microRNA...

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online