Antitumor effects of circ-EPHB4 in hepatocellular carcinoma via inhibition of HIF-1α.

The protein EPHB4 plays a vital role in various tumor types. However, few studies into the function of circ-EPHB4 (hsa_circ_0001730) in tumors have been conducted. This study aimed to investigate the functions of circ-EPHB4 and the underlying mechanism of circ-EPHB4 in regulating hepatocellular carcinoma (HCC). The expression of circ-EPHB4 was found to be downregulated in HCC tumor tissues, whereas circ-EPHB4 overexpression suppressed cell viability, induced apoptosis, and inhibited cell migration and invasion in Huh7 and HepG2 cells. circ-EPHB4 levels were negatively correlated with tumor weight, size, and metastasis foci in nude mouse models, suggesting circ-EPHB4 inhibits tumorigenesis, tumor development, and metastasis. In addition, HIF-1α and PI3K-AKT pathways were markedly affected by circ-EPHB4 overexpression. HIF-1α could potentially be the target of circ-EPHB4. By overexpressing both HIF-1α and circ-EPHB4, the antitumor effect of circ-EPHB4 should be most probably correlated with HIF-1α. In conclusion, circ-EPHB4 is a tumor inhibitor in HCC and functions by inhibiting HIF-1α expression.