title: Bmi-1 is essential for the oncogenic potential in CD133(+) human laryngeal cancer cells.
abstract: It has been hypothesized that cancer stem cells (CSCs) are a principal culprit of tumor initiation, invasion, metastasis, and treatment resistance. Previous studies have confirmed that cancer stem cells can be detected in laryngeal carcinoma. This study aimed to evaluate whether population of CD133(+) cells that existed in primary human laryngeal carcinoma have characteristic of CSCs with enhanced capacity of proliferation and invasion, and to understand whether and how Bmi-1 implicated in self-renewal and tumorigenesis. We clarified the tumorigenic potential of CD133 sorted populations of cancer cells derived from primary human laryngeal tumor sample. After fluorescence activated cell sorting, real-time polymerase chain reaction (PCR) and western blot confirmed Bmi-1 was differentially expressed in CD133 sorted laryngeal tumor cells. Bmi-1 was knocked down, and proliferation, colony formation, invasion, cell cycle assay, and apoptosis assays were performed, and the impact on Bmi-1 pathway was evaluated. It was found that CD133(+) cells existed in primary human laryngeal tumor with enhanced capacity of proliferation and invasion. Bmi-1, implicated in self-renewal and tumorigenesis, was coexpressed with the CD133. Furthermore, knockdown of Bmi-1 expression in CD133(+) cells led to inhibition of cell growth, colony formation, cell invasion in vitro, and tumorigenesis in vivo, through up-regulation of p16(INK4A) and p14(ARF). Our data indicate that Bmi-1 expression is central to the tumorigenicity of CD133(+) cells, which functions as a pleiotropic regulator that maintains the viability and proliferative capacity of human laryngeal tumor. It negatively regulates the transcription of the downstream INK4a/ARF gene and inhibits expression of P16(ink4a)/P14(ARF), so as to maintain the high ability of proliferation and differentiation in laryngeal cancer stem cells.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gansu Province, Gansu Provincial Hospital, 204 DongGangXiLu Road, 730000, Lanzhou, China. 1806799723@qq.com.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gansu Province, Gansu Provincial Hospital, 204 DongGangXiLu Road, 730000, Lanzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Pathophysiology, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gansu Province, Gansu Provincial Hospital, 204 DongGangXiLu Road, 730000, Lanzhou, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gansu Province, Gansu Provincial Hospital, 204 DongGangXiLu Road, 730000, Lanzhou, China.
authors.forename: Bingjuan
authors.initials: B
authors.lastname: Ma
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D014411:Neoplastic Stem Cells / Q000473:pathology; D010455:Peptides / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C069077:BMI1 protein, human; D006023:Glycoproteins; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D063150:Polycomb Repressive Complex 1
keywords: Bmi-1 gene; Cancer stem cells; Laryngeal carcinoma