HYOU1 promotes cell growth and metastasis via activating PI3K/AKT signaling in epithelial ovarian cancer and predicts poor prognosis

摘要

OBJECTIVE: Hypoxia upregulated 1 (HYOU1) has been reported to be abnormally expressed in different malignancies, especially in breast cancer. However, the role of HYOU1 in epithelial ovarian cancer (EOC) remains largely unclear. This study aimed to explore the expression and function of HYOU1 in EOC progression. PATIENTS AND METHODS: HYOU1 levels in EOC tissues and cell lines were investigated by RT-PCR. The clinical and prognostic significance of HYOU1 in 127 cases of EOC was analyzed using the Chi-square analysis, Kaplan-Meier analysis, and the Cox proportional hazards regression model. We have also performed multiple cells experiments to evaluate the effects of HYOU1 on EOC cell proliferation, apoptosis, migration, and invasion. The protein levels of associated PI3K/Akt signaling pathway was detected using Western blot assay. RESULTS: We found that the expression levels of HYOU1 were significantly upregulated in both EOC tissues and cell lines. A higher expression of HYOU1 was associated with advanced FIGO stage, LN metastasis, and shorter overall survival. In addition, univariate and multivariate analysis identified high HYOU1 expression as an unfavorable prognostic factor for overall survival. Functional assays revealed that the inhibition of HYOU1 suppressed the tumor proliferation and colony formation, as well as the migratory and invasive capacity. Finally, when HYOU1 was silenced, the results of Western blot showed that the levels of p-PI3K, p-Akt, as well as cell cycle and EMT genes, were respectively downregulated. CONCLUSIONS: Our findings highlighted the targeting of HYOU1 as a novel therapeutic approach for the treatment of EOC.