title: shRNA-Mediated Silencing of Y-Box Binding Protein-1 (YB-1) Suppresses Growth of Neuroblastoma Cell SH-SY5Y In Vitro and In Vivo.
abstract: Y-box binding protein-1 (YB-1), a member of cold-shock protein superfamily, has been demonstrated to be associated with tumor malignancy, and is proposed as a prognostic marker in multiple carcinomas. However, the role of YB-1 in neuroblastoma has not been well studied. To investigate the functional role of YB-1 in neuroblastoma, we established a YB-1-silenced neuroblastoma cell strain by inhibiting YB-1 expression using a shRNA knockdown approach. YB-1-silenced neuroblastoma SH-SY5Y cells exhibited a pronounced reduction in cell proliferation and an increased rate of apoptosis in vitro and in vivo xenograft tumor model. At molecular level, YB-1 silencing resulted in downregulation of Cyclin A, Cyclin D1 and Bcl-2, as well as upregulated levels of Bax, cleaved caspase-3 and cleaved PARP-1. We further demonstrated that YB-1 transcriptionally regulated Cyclin D1 expression by chromatin-immunoprecipitation and luciferase reporter assays. In addition, xenograft tumors derived from neuroblastoma SH-SY5Y cell line were treated with YB-1 shRNA plasmids by intra-tumor injection, and YB-1 targeting effectively inhibited tumor growth and induced cell death. In summary, our findings suggest that YB-1 plays a critical role in neuroblastoma development, and it may serve as a potential target for neuroblastoma therapy.
authors.affiliation: Department of Pediatric Hematology/Oncology, Hematology Center, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pediatric Hematology/Oncology, Hematology Center, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Ruowen
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Pediatric Hematology/Oncology, Hematology Center, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Gu
authors.affiliation: Department of Pediatric Hematology/Oncology, Hematology Center, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pediatric Hematology/Oncology, Hematology Center, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Hematology/Oncology, Hematology Center, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Zuofei
authors.initials: Z
authors.lastname: Chi
authors.affiliation: Department of Pediatric Hematology/Oncology, Hematology Center, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Liangchun
authors.initials: L
authors.lastname: Hao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics*; D014158:Transcription, Genetic; D051840:Y-Box-Binding Protein 1 / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D019938:Cyclin D1