Department of Urology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Division of Urology, Taipei City Hospital Heping Fuyou Branch, Taipei, Taiwan.
Cell Death Dis. 2019 Jan 10;10(1):31. doi: 10.1038/s41419-018-1241-2.
Resistin is an adipokine that is associated with obesity, inflammation, and various cancers. Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. VEGF-A is a critical angiogenic factor that is known to promote angiogenesis and metastasis in chondrosarcoma. It is unknown as to whether resistin affects human chondrosarcoma angiogenesis. In this study, we show how resistin promotes VEGF-A expression and subsequently induces angiogenesis of endothelial progenitor cells (EPCs). Resistin treatment activated the phosphatidylinositol-3-kinase (PI3K) and Akt signaling pathways, while PI3K and Akt inhibitors or siRNA diminished resistin-induced VEGF-A expression. In vitro and in vivo studies revealed the downregulation of micro RNA (miR)-16-5p in resistin-induced VEGF-A expression and EPCs angiogenesis. We also found a positive correlation between resistin and VEGF-A expression, and a negative correlation between resistin and VEGF-A with miR-16-5p in chondrosarcoma patients. These findings reveal that resistin facilitates VEGF-A expression and angiogenesis through the inhibition of miR-16-5p expression via PI3K/Akt signaling cascades. Resistin may be a promising target in chondrosarcoma angiogenesis.
抵抗素是一种与肥胖、炎症和各种癌症相关的脂肪细胞因子。软骨肉瘤是一种主要的恶性骨肿瘤，预后不良。VEGF-A 是一种关键的血管生成因子，已知可促进软骨肉瘤的血管生成和转移。目前尚不清楚抵抗素是否会影响人类软骨肉瘤的血管生成。在这项研究中，我们展示了抵抗素如何促进 VEGF-A 的表达，进而诱导内皮祖细胞 (EPC) 的血管生成。抵抗素处理激活了磷脂酰肌醇-3-激酶 (PI3K) 和 Akt 信号通路，而 PI3K 和 Akt 抑制剂或 siRNA 则减弱了抵抗素诱导的 VEGF-A 表达。体外和体内研究揭示了 miR-16-5p 在抵抗素诱导的 VEGF-A 表达和 EPC 血管生成中的下调。我们还发现软骨肉瘤患者中抵抗素与 VEGF-A 表达呈正相关，与 miR-16-5p 呈负相关。这些发现表明，抵抗素通过 PI3K/Akt 信号级联抑制 miR-16-5p 的表达，从而促进 VEGF-A 的表达和血管生成。抵抗素可能是软骨肉瘤血管生成的一个有前途的靶点。
