TXNDC5 (
thioredoxin domain-containing
protein 5) catalyzes
disulfide bond formation, isomerization and reduction. Studies have reported that TXNDC5 expression is increased in some
tumor tissues and that its increased expression can predict a poor prognosis. However, the tumorigenic mechanism has not been well characterized. In this study, we detected a significant association between the rs408014 and rs7771314 SNPs at the TXNDC5 locus and cervical
carcinoma using the Taqman genotyping method. We also detected a significantly increased expression of TXNDC5 in cervical
tumor tissues using immunohistochemistry and Western blot analysis. Additionally, inhibition of TXNDC5 expression using
siRNA prevented tube-like structure formation, an experimental
indicator of vasculogenic mimicry and
metastasis, in HeLa cervical
tumor cells. Inhibiting TXNDC5 expression simultaneously led to the increased expression of SERPINF1 (
serpin peptidase inhibitor, clade F) and
TRAF1 (
TNF receptor-associated factor 1), which have been reported to inhibit angiogenesis and
metastasis as well as induce apoptosis. This finding was confirmed in Caski and C-33A cervical tumor cell lines. The ability to form tube-like structures was rescued in HeLa cells simultaneously treated with anti-TXNDC5, SERPINF1 and
TRAF1 siRNAs. Furthermore, the inhibition of TXNDC5 expression significantly attenuated endothelial tube formation, a marker of angiogenesis, in human umbilical vein endothelial cells. The present study suggests that TXNDC5 is a susceptibility gene in
cervical cancer, and high expression of this gene contributes to abnormal angiogenesis, vasculogenic mimicry and
metastasis by down-regulating SERPINF1 and
TRAF1 expression.