PMID- 26573774 OWN - NLM STAT- MEDLINE DCOM- 20160930 LR - 20190221 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 35 IP - 2 DP - 2016 Feb TI - Downregulation of Bmi-1 is associated with suppressed tumorigenesis and induced apoptosis in CD44(+) nasopharyngeal carcinoma cancer stem-like cells. PG - 923-31 LID - 10.3892/or.2015.4414 [doi] AB - 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 fl ow 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. FAU - Xu, Xinhua AU - Xu X AD - 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. FAU - Liu, Yang AU - Liu Y AD - 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. FAU - Su, Jin AU - Su J AD - Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China. FAU - Li, Daojun AU - Li D AD - Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China. FAU - Hu, Juan AU - Hu J AD - Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China. FAU - Huang, Qiao AU - Huang Q AD - Oncology Institute, China Three Gorges University, Yichang, Hubei 443003, P.R. China. FAU - Lu, Mingqian AU - Lu M AD - 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. FAU - Liu, Xiaoyan AU - Liu X AD - 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. FAU - Ren, Jinghua AU - Ren J AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China. FAU - Chen, Weihong AU - Chen W AD - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China. FAU - Sun, Lidan AU - Sun L AD - Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Department of Medical College, China Three Gorges University, Yichang, Hubei 443002, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151112 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (BMI1 protein, human) RN - 0 (CD44 protein, human) RN - 0 (Hyaluronan Receptors) RN - 0 (RNA, Small Interfering) RN - EC 2.3.2.27 (Polycomb Repressive Complex 1) SB - IM MH - Animals MH - Apoptosis/*physiology MH - Carcinogenesis/*metabolism MH - Carcinoma MH - Cell Line, Tumor MH - Cell Proliferation/physiology MH - Down-Regulation MH - Flow Cytometry MH - Gene Knockdown Techniques MH - Heterografts MH - Humans MH - Hyaluronan Receptors/metabolism MH - Immunohistochemistry MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Nasopharyngeal Carcinoma MH - Nasopharyngeal Neoplasms/metabolism/*pathology MH - Neoplastic Stem Cells/*metabolism MH - Polycomb Repressive Complex 1/*metabolism MH - RNA, Small Interfering EDAT- 2015/11/18 06:00 MHDA- 2016/10/01 06:00 CRDT- 2015/11/18 06:00 PHST- 2015/07/16 00:00 [received] PHST- 2015/09/29 00:00 [accepted] PHST- 2015/11/18 06:00 [entrez] PHST- 2015/11/18 06:00 [pubmed] PHST- 2016/10/01 06:00 [medline] AID - 10.3892/or.2015.4414 [doi] PST - ppublish SO - Oncol Rep. 2016 Feb;35(2):923-31. doi: 10.3892/or.2015.4414. Epub 2015 Nov 12.