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Research Paper

Bmi-1 expression modulates non-small cell lung cancer progression

, , , , , , , , , & show all
Pages 756-763 | Received 09 Oct 2014, Accepted 01 Mar 2015, Published online: 16 Apr 2015
 

Abstract

Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

Research in the authors' laboratory is supported by the National Natural funding of China (81071747, 81272404), National key program (973) for Basic Research of China (2011CB510106, 2011CB504300), the Program for Professor of Special Appointment (Eastern Scholar to J, Wang) at Shanghai Institutions of Higher Learning, and Program of Shanghai Municipal Health Bureau Subject Chief Scientist (XBR20110052).

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