title: RNA interference-mediated knockdown of Livin suppresses cell proliferation and invasion and enhances the chemosensitivity to cisplatin in human osteosarcoma cells.
abstract: Livin is a novel member of the inhibitor of apoptosis protein (IAP) family that has been reported to be overexpressed in a variety of human malignancies, including osteosarcoma. However, the potential roles of Livin in tumorigenesis have not been elucidated. In the present study, we employed RNA interference (RNAi) technology to suppress endogenous Livin expression in osteosarcoma cells and successfully generated a U2-OS cell line with stably knockdown of Livin. Functional analysis showed that knockdown of Livin significantly reduced cell proliferation, colony formation, and invasion and migration capacities of U2-OS cells in vitro. Moreover, specific downregulation of Livin led to cell cycle arrest at the G0/G1 phase and eventual apoptosis. Meanwhile, western blot analysis revealed that cells with stably knockdown of Livin showed decreased expression levels of Cyclin D1, Bcl-2, matrix metalloproteinase (MMP)-2 and MMP-9, but increased expression levels of activated Caspase-3, Bax and cleaved poly (ADP-ribose) polymerase (PARP) compared to those transfected with a control vector. We also observed that suppression of Livin expression in osteosarcoma cells increased their chemosensitivity to cisplatin. Taken together, our data suggest that Livin is involved in tumorigenesis of human osteosarcoma and may serve as a promising therapeutic target for osteosarcoma.
authors: Department of Orthopaedic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Xu
authors: X
authors: Li
authors: Shuli
authors: S
authors: Fan
authors: Leiming
authors: L
authors: Li
authors: Liguo
authors: L
authors: Wang
authors: Guangyu
authors: G
authors: Fan
authors: Qun
authors: Q
authors: Zhao
authors: Yan
authors: Y
authors: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D034622:RNA Interference
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D002945:Cisplatin