title: Bmi-1 expression modulates non-small cell lung cancer progression.
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.
authors.affiliation: a Department of Biochemistry and Molecular & Cell Biology; Shanghai Key Laboratory of Tumor Microenvironment and Inflammation ; Shanghai Jiaotong University School of Medicine ; Shanghai , PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xiong
authors.forename: Yunlin
authors.initials: Y
authors.lastname: Ye
authors.forename: Yujie
authors.initials: Y
authors.lastname: Fu
authors.forename: Jinglong
authors.initials: J
authors.lastname: Wang
authors.forename: Bohua
authors.initials: B
authors.lastname: Kuang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.forename: Xiumin
authors.initials: X
authors.lastname: Wang
authors.forename: Lidong
authors.initials: L
authors.lastname: Zu
authors.forename: Gang
authors.initials: G
authors.lastname: Xiao
authors.forename: Mingang
authors.initials: M
authors.lastname: Hao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046228:Microarray Analysis; D008875:Middle Aged; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C069077:BMI1 protein, human; D063150:Polycomb Repressive Complex 1
keywords: Bmi-1; Bmi-1, B lymphoma Mo-MLV insertion region 1 homolog; EMT; EMT, epithelial-mesenchymal transition; FBS, fetal calf serum; IHC, immunohistochemistry; NSCLC; NSCLC, non-small cell lung cancer; invasion; metastasis; progression; qRT-PCR, quantitative real-time PCR.