Studies have demonstrated that small interfering RNA (siRNA) targeting YKL-40 (siYKL-40) inhibits the proliferation, migration, invasion, and induces antiapoptotic abilities of endometrial cancer (EC) HEC-1A cells. However, its effect on angiogenesis is unclear. The present study aimed to investigate the role of YKL-40 in endometrial cancer and the related molecular mechanisms. YKL-40 was knocked down by transfection with siYKL-40 and the effects on angiogenesis, cell viability, and signaling pathways were investigated. The results showed that siYKL-40 inhibited VEGFA levels and tube formation in endothelial cells. Additionally, inhibition of YKL-40 decreased the expression levels of vascular endothelial growth factor (VEGF), phosphorylated vascular endothelial growth factor receptor 2 (pVEGFR2), and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2). Furthermore, a nude mice xenograft model of EC showed that siYKL-40 inhibited tumor growth. Inhibition of YKL-40 led to suppression of angiogenesis and reduction of microvessel density through VEGF/VEGFR2 and ERK1/2 signaling in endometrial cancer cells. Taken together, this study demonstrated novel molecular mechanisms for role of YKL-40 in EC.

中文翻译：

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敲除 YKL-40 通过调节子宫内膜癌中的 VEGF/VEGFR2 和 ERK1/2 信号通路抑制血管生成

研究表明，靶向YKL-40 (si YKL-40 ) 的小干扰 RNA (siRNA)可抑制子宫内膜癌 (EC) HEC-1A 细胞的增殖、迁移、侵袭并诱导抗凋亡能力。然而，其对血管生成的影响尚不清楚。本研究旨在探讨YKL-40在子宫内膜癌中的作用及其相关分子机制。通过转染 si YKL-40敲低YKL-40 ，并研究其对血管生成、细胞活力和信号通路的影响。结果显示si YKL-40抑制内皮细胞的VEGFA水平和管形成。此外，抑制YKL-40降低血管内皮生长因子 (VEGF)、磷酸化血管内皮生长因子受体 2 (pVEGFR2) 和磷酸化细胞外信号调节激酶 1 和 2 (pERK1/2) 的表达水平。此外，EC的裸鼠异种移植模型显示si YKL-40抑制肿瘤生长。YKL-40的抑制作用通过子宫内膜癌细胞中的 VEGF/VEGFR2 和 ERK1/2 信号传导抑制血管生成和降低微血管密度。总之，本研究证明了YKL-40在 EC 中作用的新分子机制。