title: The role and clinical significance of YES-associated protein 1 in human osteosarcoma.
abstract: Yes-associated protein 1 (YAP1) is an oncogene that plays multiple roles in the tumorigenesis and progression of many malignances. The present study aimed to investigate the clinical significance of YAP1 expression in human osteosarcoma (OS) and explore the molecular mechanisms of YAP1 activity in OS MG-63 cells. The expression of YAP1 was assessed by immunohistochemical assay using a tissue microarray procedure. A loss-of-function approach was used to investigate the effects of small hairpin RNA-mediated knockdown of YAP1 on the expression of RUNX2, CyclinD1, and matrix metalloproteinase-9 (MMP-9) as well as the proliferative activities and invasive potential in OS MG-63 cells (evaluated by MTT and Transwell assays, respectively). The expression of YAP1 protein in OS tissues was significantly higher than that in ANCT, and was closely associated with gender (P = 0.013) and Enneking staging (P = 0.035), but it did not correlate with age, tumor location, or distant metastases of OS patients (P greater than 0.05, each). Knockdown of YAP1 resulted in downregulation of the expression of RUNX2, CyclinD1, and MMP-9 and inhibited the proliferation and invasion of MG-63 cells. Our findings suggest that YAP1 is highly expressed in OS tissues, and increased expression of this molecule is correlated with the gender and Enneking staging of osteosarcoma patients. Knockdown of YAP1 may inhibit the proliferation and invasion of OS cells through downregulation of the RUNX2 pathway, thereby representing a potential therapeutic target for the treatment of cancer.
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: X-D
authors.initials: XD
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D046888:Tissue Array Analysis; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C530104:CCND1 protein, human; D050659:Core Binding Factor Alpha 1 Subunit; D010750:Phosphoproteins; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D019938:Cyclin D1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9