WISP-3 inhibition of miR-452 promotes VEGF-A expression in chondrosarcoma cells and induces endothelial progenitor cells angiogenesis.

WISP-3 inhibition of miR-452 promotes VEGF-A expression in chondrosarcoma cells and induces endothelial progenitor cells angiogenesis.
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DOI:
10.18632/oncotarget.17142
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发表时间:
2017-06-13
期刊:
影响因子:
--
通讯作者:
Tang CH
Tang CH
中科院分区:
其他
文献类型:
--
作者:
Lin CY;Tzeng HE;Li TM;Chen HT;Lee Y;Yang YC;Wang SW;Yang WH;Tang CH

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软骨肉瘤是继骨肉瘤之后第二常见的骨原发肿瘤。软骨肉瘤的发展可能与血管生成有关,血管生成主要由血管内皮生长因子- a (VEGF-A)引发。VEGF-A水平已被认为是血管生成的预后指标。wnt1诱导的信号通路蛋白-3 (WISP)-3/CCN6属于CCN家族,参与调节多种细胞功能,包括细胞增殖、分化和迁移。然而,WISP-3对人软骨肉瘤中VEGF-A生成和血管生成的影响在很大程度上仍然未知。目前的研究表明,WISP-3促进了VEGF-A的产生,诱导了人内皮祖细胞的血管生成。此外,WISP-3增强的VEGF-A表达和血管生成涉及c-Src和p38信号通路,而miR-452的表达受到WISP-3通过c-Src和p38信号通路的负面影响。我们的研究结果说明了WISP-3、VEGF-A和miR-452在人软骨肉瘤患者中的临床意义。WISP-3可能是软骨肉瘤转移和血管生成的一个新的治疗靶点。
Chondrosarcoma is the second most prevalent general primary tumor of bone following osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). VEGF-A level has been recognized as a prognostic marker in angiogenesis. WNT1-inducible signaling pathway protein-3 (WISP)-3/CCN6 belongs to the CCN family and is involved in regulating several cellular functions, including cell proliferation, differentiation, and migration. Nevertheless, the effect of WISP-3 on VEGF-A production and angiogenesis in human chondrosarcoma remains largely unknown. This current study shows that WISP-3 promoted VEGF-A production and induced angiogenesis of human endothelial progenitor cells. Moreover, WISP-3-enhanced VEGF-A expression and angiogenesis involved the c-Src and p38 signaling pathways, while miR-452 expression was negatively affected by WISP-3 via the c-Src and p38 pathways. Our results illustrate the clinical significance of WISP-3, VEGF-A and miR-452 in human chondrosarcoma patients. WISP-3 may illustrate a novel therapeutic target in the metastasis and angiogenesis of chondrosarcoma.
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