Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 7, Issue 6, Pages 805-814Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.7.805
Keywords
miR-7; BCL-2; non-small cell lung cancer; A549 cells; apoptosis
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Funding
- National Key Technologies R & D Program of China [2009ZX10004-104]
- Fudan University
- National 973 project [2010CB912603, 2011CB910404]
- National Science Foundation of China [30872378, 81072408]
- Science and Technology Commission of Shanghai Municipality in China [10JC1401100]
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MicroRNAs(miRNAs) are emerging as important regulators in tumorigenesis. Increasing evidences have indicated microRNA-7(miR-7) to be a potential tumor suppressor in several human cancers. However, only a limited number of target genes have been identified so far and its biological function in Non-Small Cell Lung Cancer (NSCLC) remains to be further elucidated. In the present study, we observed a reduction of miR-7 level in NSCLC cell lines. Overexpression of miR-7 not only suppressed NSCLC A549 cells proliferation, induced cell apoptosis and inhibited cell migration in vitro, but also reduced tumorigenicity in vivo. Bioinformatics predictions revealed a potential binding site of miR-7 on 3'UTR of BCL-2 and it was further confirmed by luciferase assay. Moreover, subsequent experiments showed that BCL-2 was downregulated by miR-7 at both transcriptional and translational levels. These results suggest that miR-7 regulates the expression of BCL-2 through direct 3'UTR interactions. Therefore, we postulate BCL-2 to be a novel target possibly involved in miR-7-mediated growth suppression and apoptosis of A549 cells. These findings may provide a basic rationale for the use of miR-7 in the treatment of NSCLC.
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