TSGA10 overexpression inhibits angiogenesis of HUVECs: A HIF-2α biased perspective

Testis-specific gene antigen 10 (TSGA10) is a protein overexpressed in most cancers; except for some certain types where its expression is reduced. TSGA10 overexpression in HeLa cells has been shown to disrupt hypoxia inducible factor-1 alpha (HIF-1 alpha) axis and exert potent inhibitory effects. Since HIF-1 alpha is structurally and biochemically similar to HIF-2 alpha, TSGA10 is expected to bind HIF-2 alpha and inhibit its function as well. This study elucidated that increased expression of TSGA10 in manipulated human umbilical vein endothelial cells (HUVECs) decreased the proliferation and migration of these cells as affirmed by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) and wound healing tests, respectively. It also inhibited in vitro angiogenesis of these cells in 3D collagen-cytodex model. Expression levels of genes controlled by HIF-2 alpha including autocrine vascular endothelial growth factor (VEGF) were also assessed using real-time PCR. Our bioinformatic analysis also showed that TSGA10 could bind HIF-2 alpha. Moreover, flow cytometry results indicated a cell cycle arrest in G2/M. Therefore, this study showed that overexpression of TSGA10, as a tumor suppressor gene, in endothelial cells resulted in decreased proliferation, migration and therefore, angiogenic activity of HUVECs. Since angiogenesis is vital for tumor development and metastasis, our findings could be of clinical significance in cancer therapy.