title: Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma.
abstract: Osteosarcoma is a common malignant bone tumor in children and adolescents. The current 5-year survival rate is ~60% and that seems to be reaching a plateau. In order to improve treatment outcomes of osteosarcoma, a better understanding of tumorigenesis and underlying molecular mechanisms is required for searching out possible new treatment targets. This study aimed to identify the potential proteins involving the pathogenesis of osteosarcoma using a proteomics approach. Proteins extracted from primary cell culture of osteosarcoma (n=7) and osteoblasts of cancellous bone (n=7) were studied. Using 2-DE based proteomics and LC-MS/MS analysis, we successfully determined seven differentially expressed protein spots. Four upregulated proteins and three downregulated proteins were observed in this study in which KH-type splicing regulatory protein (KSRP) was selected for further exploration. KSRP was significantly upregulated in osteosarcoma cells compared to osteoblasts using western blot assay. In addition, immunohistochemistry demonstrated that KSRP was also highly expressed in osteosarcoma tissue of independent cases from the experimental group. More importantly, KSRP silencing of osteosarcoma cell lines significantly decreased cell proliferation, migration ability, as well as implantation and growth ability in chick chorioallantoic membrane assay. Taken together, these findings demonstrate, that KSRP plays important roles in regulatory controls of osteosarcoma pathogenesis and serves as a potentially therapeutic target of osteosarcoma.
authors: Department of Orthopedics, Faculty of Medicine, Orthopedic Laboratory and Research Netting Center (OLARN Center), Chiang Mai University, Chiang Mai 50200, Thailand.
authors: Dumnoensun
authors: D
authors: Pruksakorn
authors: Department of Orthopedics, Faculty of Medicine, Orthopedic Laboratory and Research Netting Center (OLARN Center), Chiang Mai University, Chiang Mai 50200, Thailand.
authors: Pimpisa
authors: P
authors: Teeyakasem
authors: Department of Orthopedics, Faculty of Medicine, Orthopedic Laboratory and Research Netting Center (OLARN Center), Chiang Mai University, Chiang Mai 50200, Thailand.
authors: Jeerawan
authors: J
authors: Klangjorhor
authors: Department of Orthopedics, Faculty of Medicine, Orthopedic Laboratory and Research Netting Center (OLARN Center), Chiang Mai University, Chiang Mai 50200, Thailand.
authors: Parunya
authors: P
authors: Chaiyawat
authors: Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors: Jongkolnee
authors: J
authors: Settakorn
authors: Biochemistry Laboratory, Chulabhorn Research Institute, Bangkok 10210, Thailand.
authors: Penchatr
authors: P
authors: Diskul-Na-Ayudthaya
authors: Biochemistry Laboratory, Chulabhorn Research Institute, Bangkok 10210, Thailand.
authors: Daranee
authors: D
authors: Chokchaichamnankit
authors: Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors: Peraphan
authors: P
authors: Pothacharoen
authors: Biochemistry Laboratory, Chulabhorn Research Institute, Bangkok 10210, Thailand.
authors: Chantragan
authors: C
authors: Srisomsap
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D002648:Child; D002675:Child, Preschool; D049033:Chorioallantoic Membrane / Q000473:pathology; D002853:Chromatography, Liquid; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000473:pathology*; D040901:Proteomics / Q000379:methods*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C105789:KHSRP protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators