HERC4 modulates ovarian cancer cell proliferation by regulating SMO-elicited hedgehog signaling

HERC4 has been reported to have functions in several types of tumors, but its roles in ovarian cancer have not been studied yet. Primary tissues from ovarian cancer patients and cell lines were collected for real-time PCR. Kaplan-Meier Plotter was used to predict the prognosis of ovarian cancer patients. HERC4 was overexpressed in cells by lentivirus, and CCK-8 assay was performed to evaluate cell viability. Real-time PCR and Western blot were carried out to analyze the mRNA and protein expression, respectively. Xenograft tumor models were established to analyze HERC4 function in vivo. Firstly, we found that HERC4 was significantly downregulated in ovarian cancer. We then found that ovarian cancer patients with high HERC4 expression had significantly higher overall survival and progression-free survival rates compared with patients with low expression. Then, HERC4 was overexpressed in ovarian cancer cells, and we found that overexpression of HERC4 significantly inhibited ovarian cancer cell growth, as well as the expression of the target protein SMO, and the key proteins in the downstream hedgehog signaling pathway. Finally, the xenograft tumor models revealed that overexpression of HERC4 significantly inhibited tumor growth in vivo. Overall, these results indicate that overexpression of HERC4 inhibits cell proliferation of ovarian cancer in vitro and in vivo, suggesting that HERC4 may serve as an effective target for the treatment of ovarian cancer. •HERC4 is significantly downregulated in ovarian cancer compared to non-cancer cell lines.•A significant downregulation of HERC4 in 5 ovarian cancer cell lines•HERC4 inhibited ovarian cancer occurrence both in vitro and in vivo.