title: Silencing Bmi-1 expression by RNA interference suppresses the growth of laryngeal carcinoma cells.
abstract: The aim of this study was to investigate the effect of a B-cell-specific MLV integration site-1 (Bmi-1) RNA interference (RNAi) expression vector on the proliferation and invasiveness of laryngeal carcinoma. We constructed a lentiviral vector expressing Bmi-1-specific short hairpin RNA (shRNA), and transfected it into HEp-2 cells. Bmi-1 gene expression was detected by real-time RT-PCR and western blot analysis. We used flow cytometry and TUNEL assay to analyze the apoptosis of transfected cells, and examined cellular growth in vitro by MTT assay. We established an animal model and evaluated the therapeutic effects of small interfering RNA (siRNA) against Bmi-1. siRNA against Bmi-1 significantly knocked down Bmi-1 expression in HEp-2 cells, induced cell cycle arrest at the G1 phase, inhibited cell proliferation and promoted cell apoptosis. Lentiviral Bmi-1-shRNA vector transfection also significantly reduced cell migration. The formation and growth rate of xenograft tumors in mice transfected with siRNA against Bmi-1 was significantly reduced. The loss of mitochondrial membrane potential, the release of cytochrome c from the mitochondria into the cytosol, and the increased activity of caspase-3, -8 and -9 occurred concomitantly with the inhibition of Bmi-1. Our data indicate that siRNA against Bmi-1 significantly suppresses tumor growth and induces apoptosis in vitro and in vivo.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China. xiaobaoyaocn@126.com
authors.forename: Xiao-Bao
authors.initials: XB
authors.lastname: Yao
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Shao-Qiang
authors.initials: SQ
authors.lastname: Zhang
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D003124:Colorimetry; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007822:Laryngeal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D016086:Lentivirus / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D014945:Wound Healing / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C069077:BMI1 protein, human; D018076:DNA, Complementary; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1; D020169:Caspases