title: shRNA-mediated knockdown of Bmi-1 inhibit lung adenocarcinoma cell migration and metastasis.
abstract: Bmi-1 has been implicated in cancer cell growth and metastasis in a variety of tumor types. In this study, we sought to evaluate the expression of Bmi-1 in lung adenocarcinoma samples, and to determine if a correlation exists between Bmi-1 expression and clinical features of lung cancer, such as metastasis. Our results showed that Bmi-1 expression is increased in lung cancer tissues compared to adjacent non-cancerous tissues, and is associated with clinical features of lung cancer, including clinical stage and distant metastasis. We were then interested in determining if shRNA-mediated knockdown of Bmi-1 would inhibit metastasis of lung adenocarcinoma cells. To this end, we chose the most efficient shRNA duplexes targeting Bmi-1, and constructed two stably transfected lung adenocarcinoma cell lines (A549 and SPCA1). The shRNA-mediated knockdown of Bmi-1 significantly reduced migration in vitro, and metastasis in vivo, of A549 and SPCA1 cells. More importantly, knockdown of Bmi-1 also upregulated PTEN expression, and downregulated p-Akt and VEGF expression. These data support the hypothesis that Bmi-1 regulates key pathways involved in the metastasis of lung adenocarcinoma cells.
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian, Liaoning 116029, China.
authors.forename: Xiuxiang
authors.initials: X
authors.lastname: Meng
authors.forename: Yifang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zheng
authors.forename: Chunqing
authors.initials: C
authors.lastname: Liu
authors.forename: Benli
authors.initials: B
authors.lastname: Su
authors.forename: Huiling
authors.initials: H
authors.lastname: Nie
authors.forename: Baoxia
authors.initials: B
authors.lastname: Zhao
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D063150:Polycomb Repressive Complex 1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human