The genetic aberrations of vascular endothelial growth factor (VEGF), mammalian target of rapamycin, Wnt signaling pathway, the inactivation of p53, Rb, WWOX genes, and amplification of APEX1, c-myc, RECQL4, RPL8, MDM2, VEGFA might be involved in the pathogenesis of osteosarcoma.
According to Cox regression analysis, the VEGF+1612A/G, -634G/C, and +936T/C polymorphisms did not statistically significantly increase the risk of overall survival of patients with osteosarcoma.
Here, we screened an OS cell-specific aptamer (LC09) and developed a LC09-functionalized PEG-PEI-Cholesterol (PPC) lipopolymer encapsulating CRISPR/Cas9 plasmids encoding VEGFA gRNA and Cas9.
The pooled results suggested that VEGF-2578C/A polymorphism was significantly associated with osteosarcoma risk in all genetic models as well as VEGF-634G/C polymorphism.
It has been reported that VEGFR expression correlates with the outcome of patients with osteosarcoma and circulating VEGF level has been associated with the development of lung metastasis.
Moreover, the function of HIF1 in osteosarcoma cells was further investigated in in-vitro experiments by regulating HIF1 and vascular endothelial growth factor-A (VEGF-A) expression.
Cyr61 and VEGF expressions moderately correlated with each other in osteosarcoma, and exhibited significant association with Enneking stage and distant metastasis.
Transfection of human osteosarcoma 9901 and HOS cells with pSilenceApe1 resulted in a dose-dependent loss of Ape1 protein. pSilenceApe1 also significantly suppressed the expression of vascular endothelial growth factor (VEGF) protein in the 9901 cells.
These effects were associated with decreased expression of Notch-1 and its downstream genes, such as vascular endothelial growth factor and matrix metalloproteinases, as well as increased expression of a panel of tumor-suppressive microRNAs (miRNAs), including miR-34a, miR-143, miR-145 and miR-200b/c that are typically lost in osteosarcoma.
Moreover, we show that WISP-1 promotes VEGF-A expression in human osteosarcoma cells, subsequently inducing human endothelial progenitor cell (EPC) migration and tube formation.
In addition, we detected the expression of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription 3 (STAT3) in osteosarcoma cell treated with Eag1 small interfering RNAs (siRNAs).
Furthermore, the results showed that vascular endothelial growth factor (VEGF) expression was down-regulated in osteosarcoma cells after miR-145 transfection.
This study shows that CCL3 promotes VEGF-A expression and angiogenesis in human osteosarcoma cells by down-regulating miR-374b expression via JNK, ERK, and p38 signaling pathways.
We found that serum concentrations of CXCL8 and vascular endothelial growth factor were elevated in osteosarcoma patients in comparison with those in NCs.
The study demonstrates potent growth and pulmonary metastasis inhibitory effects of VEGF-siRNA on osteosarcoma in vivo and in vitro, which could potentially be applicable to the treatment of cancers as an antiangiogenic therapeutic in the near future.