FEBS2023, Tours, Fransa, 8 - 12 Temmuz 2023, ss.74
CYP2W1 is one of the newly admitted orphan CYP to the P450 family. Unlike other CYPs, CYP2W1 expression was not mainly recognized in any adult human tissues but was detected during fetal development. Contrary to the undetectable or very lowlevel expression in the nontransformed adult tissues, high levels of CYP2W1 gene and protein expressions were reported in some cancers including human colorectal cancer and hepatocellular carcinoma. Also, CYP2W1 expression is positively correlated with a more aggressive tumor phenotype. Although angiogenesis is known as a key mediator of tumor progression, possible regulatory role of CYP2W1 during this process is still unknown. In this study, the CYP2W1 gene expression was silenced in the HepG2 cell line by using small interfering RNAs and possible angiogenic function of CYP2W1 in tumorigenesis was investigated. Vascular endothelial growth factor (VEGF) is thought to be the key mediator of angiogenesis. Repression of CYP2W1 gene caused statistically significant decrease in both VEGFA mRNA expression and secreted VEGF protein level in HepG2 cells. Moreover, to determine whether the decrease in secreted VEGF functionally affects angiogenesis, endothelial tube formation assay was performed using human umbilical vein endothelial cells (HUVEC) in Matrigel. Conditioned medium obtained from CYP2W1 silencing of HepG2 cells after 48 hours didn’t result in significant changes in all the capillarylike structure formation parameters including total tube length, number of tubes, branching points and loops compared to scramble siRNA transfected cells. In our study, although silencing of CYP2W1 regulated the VEGF level, the expected functional effects of it on in vitro angiogenesis assay were not observed.