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.
[1]Shanghai Jiao Tong Univ, Shanghai Key Lab Tumor Microenvironm & Inflammat, Dept Biochem & Mol & Cell Biol, Sch Med, Shanghai 200030, Peoples R China.
[2]Fudan Univ, Dept Clin Lab, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China.
[3]Renji Hosp, Dept Thorac Surg, Shanghai, Peoples R China.
[4]Fudan Univ, Inst Canc, Shanghai Canc Ctr, Shanghai 200433, Peoples R China.
[5]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.
[6]Sun Yat Sen Univ, Ctr Canc, Dept Urol, Guangzhou 510275, Guangdong, Peoples R China.
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