Knockdown of YKL-40 inhibits angiogenesis through regulation of VEGF/VEGFR2 and ERK1/2 signaling in endometrial cancer.

ABSTRACT

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.