Abstract
Growing evidence indicates that the alteration of microRNA (miRNA) expression in tumors that is induced by chemical carcinogens plays an important role in tumor development and progression. However, the mechanism underlying miRNA involvement in lung carcinogenesis induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti-BPDE) remains unclear. In our study, we used the malignant transformation of human bronchial epithelial cells (16HBE-T) induced by anti-BPDE to explore the mechanisms of human lung carcinogenesis. We found that expression of miR-506 was reduced in 16HBE-T transformed malignant human bronchial epithelial cells compared with 16HBE normal human bronchial epithelial cells. Restoration of miR-506 in 16HBE-T cells led to a decrease in cell proliferation, G0/G1 phase cell cycle arrest, as well as significantly suppressed anchorage-dependent growth in vitro and tumor growth inhibition in a nude mouse xenograft model. In addition, we provided novel evidence regarding the role miR-506 potentially plays in negatively regulating the protein and mRNA expression level of N-Ras in cancer cells. Together, these findings revealed that miR-506 acts as an anti-oncogenic miRNA (anti-oncomir) in malignantly transformed cells. The identification of tumor suppressive miRNAs could provide new insight into the molecular mechanisms of chemical carcinogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 320-326 |
| Number of pages | 7 |
| Journal | Toxicology Letters |
| Volume | 205 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 10 2011 |
Bibliographical note
Funding Information:This work was supported by the National Natural Science Foundation of China [ 30972443 to J.Y., 30771780 to J.Y. ]; the Guangdong Natural Science Foundation [ 9251018201000004 to J.Y., 07117550 to J.Y. ]; the University Talent Program of Guangdong [ 2010-79 to J.Y.]; the Science and Technology Program of Guangzhou [ 2010Y1-C441 to J.Y.] and the University Talent Program of Guangzhou [ 10A003D to J.Y.]
Funding
This work was supported by the National Natural Science Foundation of China [ 30972443 to J.Y., 30771780 to J.Y. ]; the Guangdong Natural Science Foundation [ 9251018201000004 to J.Y., 07117550 to J.Y. ]; the University Talent Program of Guangdong [ 2010-79 to J.Y.]; the Science and Technology Program of Guangzhou [ 2010Y1-C441 to J.Y.] and the University Talent Program of Guangzhou [ 10A003D to J.Y.]
| Funders | Funder number |
|---|---|
| University Talent Program of Guangdong | 2010-79 |
| University Talent Program of Guangzhou | 10A003D |
| National Natural Science Foundation of China (NSFC) | 30771780, 30972443 |
| Natural Science Foundation of Guangdong Province | 9251018201000004, 07117550 |
| Guangzhou Science and Technology Program key projects | 2010Y1-C441 |
Keywords
- Anti-BPDE
- Cell transformation
- Human bronchial epithelial cells
- MiR-506
- MicroRNA
ASJC Scopus subject areas
- Toxicology
