title: Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44⁺ nasopharyngeal carcinoma cancer stem-like cells.
abstract: Bmi-1 (B-cell-specific Moloney murine leukemia virus insertion site 1) is a member of the Polycomb group gene (PcG) family, which is involved in the proliferation, migration and tumorigenesis of several types of cancer stem cells (CSCs). However, its precise role and mechanism in CD44+ nasopharyngeal carcinoma (NPC) cancer stem-like cells (CSC-LCs) remain poorly understood. In our previous study, we successfully silenced Bmi-1 by short hairpin RNA (shRNA) in CD44+ NPC CSC-LCs and obtained stable Bmi-1 knockdown (KD) cell lines. In the present study, we tested the cell proliferation by CCK-8 assay and apoptosis by ﬂow cytometry. Scratch wound healing assay, together with Transwell migration and invasion assays were used to measure the migration and invasion capacity. We further evaluated the tumorigenicity of CD44+ NPC CSC-LCs transfected with Bmi-1 shRNA in vivo. Based on our results, knockdown of Bmi-1 by shRNA resulted in the inhibition of tumor proliferation, migration and invasion in vitro, followed by cell apoptosis. In addition, our results preliminarily demonstrated that inhibition of Bmi-1 expression by shRNA increased tumor apoptosis through the p16INK4a-p14ARF-p53 pathway. Bmi-1 silencing in CD44+ NPC CSC-LCs also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of Bmi-1 in the occurrence and development of NPC. Based on our findings, regulation of Bmi-1 in CD44+ NPC CSC-LCs may provide a potential molecular target for the therapy of NPC, and targeted silencing of Bmi-1 by shRNA may have clinical future implications in NPC therapy.
authors.affiliation: The First College of Clinical Medical Science, China Three Gorges University and Department of Oncology, Yichang Central People's Hospital, Yichang, Hubei 443003, P.R. China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xu
authors.affiliation: The First College of Clinical Medical Science, China Three Gorges University and Department of Oncology, Yichang Central People's Hospital, Yichang, Hubei 443003, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Su
authors.affiliation: Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China.
authors.forename: Daojun
authors.initials: D
authors.lastname: Li
authors.affiliation: Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Hu
authors.affiliation: Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Huang
authors.affiliation: The First College of Clinical Medical Science, China Three Gorges University and Department of Oncology, Yichang Central People's Hospital, Yichang, Hubei 443003, P.R. China.
authors.forename: Mingqian
authors.initials: M
authors.lastname: Lu
authors.affiliation: The First College of Clinical Medical Science, China Three Gorges University and Department of Oncology, Yichang Central People's Hospital, Yichang, Hubei 443003, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Ren
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Chen
authors.affiliation: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Department of Medical College, China Three Gorges University, Yichang, Hubei 443002, P.R. China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D063646:Carcinogenesis / Q000378:metabolism*; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: C069077:BMI1 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1