Abstract
Vascular endothelial growth factor A (VEGF-A), a fundamental component of angiogenesis, provides nutrients and oxygen to solid tumors, and enhances tumor cell survival, invasion, and migration. Nuclear factor 90 (NF90), a double-stranded RNA-binding protein, is strongly expressed in several human cancers, promotes tumor growth by reducing apoptosis, and increasing cell cycle process. The mechanisms by which cervical cancer cells inducing VEGF-A expression and angiogenesis upon NF90 upregulation remain to be fully established. We demonstrated that NF90 is upregulated in human cervical cancer specimens and the expression of NF90 is paralleled with that of VEGF-A under hypoxia. The expressions of hypoxia inducible factor-1α (HIF-1α) and VEGF-A are downregulated upon NF90 knockdown, which can be rescued by ectopic expression of NF90. Suppression of NF90 decreases the tube formation and cell migration of HUVECs. Moreover, the PI3K/Akt signaling pathway participates in the regulation. Knockdown of NF90 also reduces the tumor growth and angiogenesis of cervical cancer cell line in the mouse xenograft model. Taken together, suppression of NF90 in cervical cancer cell lines can decrease VEGF-A expression, inhibit angiogenesis, and reduce tumorigenic capacity in vivo.