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    题名: WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma
    作者: 蔡筱琪;Hsiao-Chi Tsai;Huey-En Tzen;Huey-En Tzeng;Chun-Yin Hua;Chun-Yin Huang;黃元勵;HUANG, YUAN-LI;Chun-Hao Tsa;Chun-Hao Tsai;Shih-Wei Wan;Shih-Wei Wang;Po-Chuan Wan;Po-Chuan Wang;An-Chen Chan;An-Chen Chang;Yi-Chin Fong;湯智昕;Chih-Hsin Tang
    贡献者: 生物科技學系
    日期: 2017-04
    上传时间: 2017-10-30 10:41:17 (UTC+8)
    摘要: In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood. We demonstrate a positive correlation between WISP-1 and VEGF-A expression in human osteosarcoma. Moreover, we show that WISP-1 promotes VEGF-A expression in human osteosarcoma cells, subsequently inducing human endothelial progenitor cell (EPC) migration and tube formation. The focal adhesion kinase (FAK), Jun amino-terminal kinase (JNK), and hypoxia-inducible factor (HIF)-1α signaling pathways were activated after WISP-1 stimulation, while FAK, JNK, and HIF-1α inhibitors or small interfering RNA (siRNA) abolished WISP-1-induced VEGF-A expression and angiogenesis. In vitro and in vivo studies revealed down-regulation of microRNA-381 (miR-381) in WISP-1-induced VEGF-A expression and angiogenesis. Our findings reveal that WISP-1 enhances VEGF-A expression and angiogenesis through the FAK/JNK/HIF-1α signaling pathways, as well as via down-regulation of miR-381 expression. WISP-1 may be a promising target in osteosarcoma angiogenesis.
    關聯: Cell Death & Disease
    显示于类别:[生物科技學系] 期刊論文


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