title: Overexpression of X-Box Binding Protein 1 (XBP1) Correlates to Poor Prognosis and Up-Regulation of PI3K/mTOR in Human Osteosarcoma.
abstract: Increasing evidence demonstrates that dysregulation of XBP1 function contributes to tumorigenesis in some cancers. However, little is known about the role of XBP1 in the progression of osteosarcoma (OS). The expression of XBP1 in OS samples was measured by quantitative RT-PCR and Western blotting assays. Cell cycle analysis and cell counting kit 8 (CCK8) assays were performed to determine the effects of XBP1 expression on cells growth capacity. Cell apoptosis coassay was applied to determine cell survival. The expression of genes affected by XBP1 was examined by quantitative RT-RCR and validated by Western blotting assays. XBP1 was overexpressed in OS clinical samples compared with corresponding non-cancerous tissues. Overexpression of XBP1 was significantly associated with advanced clinical stages, high degree of malignancy and low tumor necrosis rate. Furthermore, hypoxia activated XBP1, and silencing XBP1 significantly enhanced OS cell apoptosis. Knock-down of XBP1 resulted in inhibition of OS growth. Most importantly, knockdown of XBP1 led to down-regulation of PIK3R3 and mTOR. Taken together, XBP1 is up-regulated and has a pro-tumor effect in OS with activation of PI3K/mTOR signaling. Thus, targeting XBP1 may provide a new potential therapeutic method for OS.
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, China. jielai1990@163.com.
authors.forename: Jielai
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, China. 18817314717@163.com.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Institute of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, China. zhoushumin168@hotmail.com.
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, China. zhubin.0526@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, China. zzuhutu@163.com.
authors.forename: Tu
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai 200233, China. tjyqc@163.com.
authors.forename: Qingcheng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D047368:Tumor Burden; D015854:Up-Regulation; D000071717:X-Box Binding Protein 1; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D000071701:Regulatory Factor X Transcription Factors; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C523442:PIK3R3 protein, human
keywords: PI3K/mTOR signaling; X-box binding protein 1; growth; osteosarcoma; survival