Department of Gynecology and Obstetrics, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital South Branch, Fuzhou, 350028, Fujian, People's Republic of China.
Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children's Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, Fujian, People's Republic of China.
Arch Gynecol Obstet. 2022 Jun;305(6):1525-1534. doi: 10.1007/s00404-021-06323-0. Epub 2021 Nov 19.
Ovarian cancer is the leading cause of death from a gynaecological malignancy in the developed world, and is characterized by invasion and metastasis and thus causes a high fatality rate. Estrogen-related receptor alpha (ERRα) has been demonstrated to play a widespread and pathophysiological relevant role in tumourigenesis and development. The aim of this study was to investigate the effect of ERRα expression on the progression of ovarian cancer.
The correlation between ERRα expression level and clinical pathological parameters in ovarian cancer tissues were analysed via cancer public database CPTAC. The expression level of ERRα in ovarian cancer cells were confirmed by RT-qPCR and Western blot methods. The cellular ERRα expression was up-regulated by lentivirus transfection and down-regulated by specific antagonist. The invasion and metastasis capabilities of ovarian cancer cells were characterized by wound healing assay and trans-well chamber assay.
The CPTAC database showed that the ERRα expression levels were higher in the late-stage and high-grade ovarian cancer tissues than in early-stage and low-grade tissues. Ovarian cancer cells with higher-expression ERRα exhibited stronger invasion and metastasis capabilities in vitro. After up-regulating the ERRα expression level, the invasion and metastasis capabilities of ovarian cancer cells were enhanced, while down-regulation weakened. Moreover, the wound sealing rate was positively correlated with the expression of ERRα mRNA expression level (r = 0.921, P < 0.01), and the cell invasiveness was also positively correlated with the cellular ERRα mRNA expression level (r = 0.926, P < 0.01).
Our results suggest that ERRα may promote the progression of ovarian cancer, and may serve as a promising predictive biomarker.
在发达国家,卵巢癌是妇科恶性肿瘤导致死亡的主要原因,其特征是侵袭和转移,因此死亡率很高。雌激素相关受体α(ERRα)已被证明在肿瘤发生和发展中具有广泛的病理生理相关作用。本研究旨在探讨 ERRα表达对卵巢癌进展的影响。
通过癌症公共数据库 CPTAC 分析 ERRα表达水平与卵巢癌组织临床病理参数的相关性。采用 RT-qPCR 和 Western blot 方法证实卵巢癌细胞中 ERRα的表达水平。通过慢病毒转染上调 ERRα的细胞表达,通过特异性拮抗剂下调 ERRα的细胞表达。通过划痕愈合试验和 Transwell 室试验来表征卵巢癌细胞的侵袭和转移能力。
CPTAC 数据库显示,晚期和高级别卵巢癌组织中的 ERRα表达水平高于早期和低级别组织。体外高表达 ERRα的卵巢癌细胞具有更强的侵袭和转移能力。上调 ERRα表达水平后,卵巢癌细胞的侵袭和转移能力增强,而下调则减弱。此外,伤口封闭率与 ERRα mRNA 表达水平呈正相关(r=0.921,P<0.01),细胞侵袭性也与细胞内 ERRα mRNA 表达水平呈正相关(r=0.926,P<0.01)。
我们的研究结果表明,ERRα可能促进卵巢癌的进展,可能成为有前途的预测生物标志物。