title: Sox9 regulates hyperexpression of Wnt1 and Fzd1 in human osteosarcoma tissues and cells.
abstract: Osteosarcoma (OS) is the most common primary malignant bone tumor that has poor prognosis. Molecular mechanisms underlying disease progression remain largely unknown. Sox9, one of the Sox family transcription factors, is closely associated with the development of a variety of malignant tumors. This study investigates the expression of Sox9, Wnt1 and Fzd1 in human osteosarcoma tissues and cells and the role of Sox9 in the proliferation of human osteosarcoma cells. Immunohistochemical analyses for Sox9, Wnt1, Fzd1, and Ki-67 proteins were performed in human primary osteosarcoma tissues from 48 patients. The small interfering RNA (siRNA) of Sox9 was transfected into human osteosarcoma MG63 cells. At 24 and 48 h after transfection with Sox9 siRNA, the expression of Wnt1 and Fzd1 was analyzed by RT-qPCR, Western blot, and immunofluorescence techniques. Cell proliferation was assayed by CCK-8 method, and Ki-67 protein expression was analyzed by Western blot. Results showed that the expressions of Sox9, Wnt1, Fzd1, and Ki-67 proteins in human osteosarcoma tissues were higher than those in the adjacent non-cancerous tissues. Hyperexpressions of Sox9, Wnt1, Fzd1, and Ki-67 proteins occurred more frequently in human osteosarcoma tissues with an advanced clinical stage (IIb/III). Sox9 siRNA reduced both mRNA and protein expression levels of Wnt1 and Fzd1, which result in the distinct inhibition of MG63 cell proliferation. Our study suggests that Sox9 siRNA inhibits the proliferation capability of human osteosarcoma cells by down-regulating the expression of Wnt1 and its receptor Fzd1, which may provide new gene targets for the clinical treatment of osteosarcoma.
authors.affiliation: Department of Orthopedics, Clinical College, Weifang Medical University Weifang, Shandong, P.R. China.
authors.forename: Huancai
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Histology and Embryology, Weifang Medical University Weifang, Shandong, P.R. China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Weifang Medical University Weifang, Shandong, P.R. China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Histology and Embryology, Weifang Medical University Weifang, Shandong, P.R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Jie
authors.affiliation: Department of Histology and Embryology, Weifang Medical University Weifang, Shandong, P.R. China.
authors.forename: Leidong
authors.initials: L
authors.lastname: Pu
authors.affiliation: Department of Histology and Embryology, Weifang Medical University Weifang, Shandong, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Medicine Research Center, Weifang Medical University Weifang, Shandong, P.R. China.
authors.forename: Fengjie
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Clinical College, Weifang Medical University Weifang, Shandong, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School Boston, Massachusetts, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Brigham and Women's Hospital and Harvard Medical School Boston, Massachusetts 02115, USA ; Harvard Stem Cell Institute, Harvard University Cambridge, Massachusetts 02138, USA.
authors.forename: Shuanhu
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics*; D002648:Child; D005260:Female; D005455:Fluorescent Antibody Technique; D051157:Frizzled Receptors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation; D051155:Wnt1 Protein / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
chemical_list: C489740:FZD1 protein, human; D051157:Frizzled Receptors; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C495247:WNT1 protein, human; D051155:Wnt1 Protein
keywords: Fzd1; MG63 cells; Osteosarcoma; Sox9; Wnt1; proliferation