HYOU1 promotes cell growth and metastasis via activating PI3K/AKT signaling in epithelial ovarian cancer and predicts poor prognosis
HYOU1 promotes cell growth and metastasis via activating PI3K/AKT signaling in epithelial ovarian cancer and predicts poor prognosis
复制标题
DOI：
10.26355/eurrev_201901_17914
复制
发表时间：
2019-05-01
影响因子：
3.3
通讯作者：
Wang, N-N
中科院分区：
文献类型：
--
作者：
Li, X.;Zhang, N-X;Wang, N-N
目的：低氧上调蛋白1（HYOU 1）在多种恶性肿瘤中异常表达，尤其是在乳腺癌中。然而，HYOU 1在上皮性卵巢癌（EOC）中的作用仍不清楚。本研究旨在探讨HYOU 1在卵巢上皮性癌中的表达及功能。患者和方法：采用RT-PCR方法检测卵巢上皮性癌组织和细胞系中HYOU 1的表达。采用卡方分析方法分析127例卵巢上皮性癌中HYOU 1基因的表达与临床及预后的关系。Kaplan-Meier分析和考克斯比例风险回归模型。我们还进行了多细胞实验以评估HYOU 1对EOC细胞增殖、凋亡、迁移和侵袭的影响。结果：HYOU 1在EOC组织和细胞系中的表达水平均显著上调，与对照组比较差异有统计学意义（P < 0. 05）。HYOU 1的高表达与FIGO分期相关。LN转移，总生存期较短。此外，单变量和多变量分析确定HYOU 1高表达是总生存率的不利预后因素。功能分析表明，抑制HYOU 1抑制肿瘤的增殖和集落形成，以及迁移和侵袭能力。Western blot结果显示，沉默HYOU 1后，p-PI 3 K的表达水平明显降低。p-Akt，以及细胞周期和EMT基因，分别下调。结论：我们的研究结果突出了HYOU 1作为治疗EOC的一种新的治疗方法的目标。
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.