shRNA targeting Bmi1 impedes the self-renewal of cisplatin-enriched             stem-like cells in human A549 cells.
It has been hypothesized that cancer stem-like cells are responsible for             tumor recurrence following chemotherapy. Evidence on the mechanisms through which             drug-resistant stem-like cells recapitulate the tumor mass has not been definitively             reported. Based on this information, we investigated the enrichment ability of             a population of stem-like cells following treatment with cisplatin in human A549             cells and focused on the molecular mechanisms regulating the self-renewal of stem-like             cells. A population of stem-like cells was enriched following cisplatin treatment             and was defined phenotypically and functionally based on the expression of certain             stem cell markers, sphere-forming ability, multipotent differentiation and induction             of xenograft tumors in vivo. For various types of differentiated cells, Bmi1 has             been reported to be important for cell proliferation and for the self-renewal             of stem cells. The high expression of Bmi1 in cisplatin-enriched stem-like cells             was shown using Q-PCR and western blotting; therefore, the role of Bmi1 was investigated             in cisplatin-enriched stem-like cells by infecting cisplatin-enriched stem-like             cells with Bmi1-targeted RNAi lentiviruses. Cell proliferation, tumor sphere formation             and xenograft formation was reduced following knockdown of Bmi1. Based on our             results, we propose that, after cisplatin treatment, Bmi1 is required for the             self-renewal of stem-like cells that are important for the expansion of the stem-like             cell pool in human A549 cells and that targeting Bmi1 slows down the formation             of tumors in vivo.
The Third Department of Oncology, PLA Cancer Research Institute of the Second Affiliated Hospital, The Third Military Medical University, Chongqing 400037, PR China.
Yu
Y
Xu
Yi-De
YD
Hu
Jing
J
Zhou
Ming-Hui
MH
Zhang
Wei-Wei
WW
Yuan
Yan
Y
Luo
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D014183:Transplantation, Heterologous
C069077:BMI1 protein, human; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1; D002945:Cisplatin