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J Cancer Res Clin Oncol. 2010 Jul;136(7):1023-8. doi: 10.1007/s00432-009-0747-5. Epub 2009 Dec 22.

The let-7a microRNA protects from growth of lung carcinoma by suppression of k-Ras and c-Myc in nude mice.

Author information

1
Department of Cell Biology and Medical Genetics, Molecular Medicine and Cancer Research Center, Chongqing Medical University, No. 1, Medical College Road, 400016 Chongqing, China.

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 immunohistochemistry 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 xenografts 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.

PMID:
20033209
DOI:
10.1007/s00432-009-0747-5
[Indexed for MEDLINE]

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