Abstract

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.

Highlights

  • Ovarian cancer is one of the most common gynecological malignancies

  • The Clinical Proteomic Tumor Analysis Consortium (CPTAC) database showed that the ERRα expression levels were higher in the late-stage and high-grade ovarian cancer tissues compared with those in early-stage and low-grade tissues

  • There was a positive correlation between the percentages of wound closure and cellular ERRα mRNA expression level (r=0.921, P

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Summary

Introduction

Ovarian cancer is one of the most common gynecological malignancies. It has a high risk of invasion and metastasis, post-treatment recurrence and drug resistance. There are about 125,000 people die of ovarian cancer every year in the world (1), so it is a serious threat to women’s lives and health. Ovarian cancer patients lack typical symptoms at the early stage, and about 70% of the cancer cases are diagnosed at the advanced stage, and the five-year survival rate is only 20–30% (2). Ovarian cancer is prone to metastasis, recurrence and poor prognosis, and present substantial challenges in its diagnosis and treatment. There is an urgent need to find promising biomarkers or therapeutic targets for ovarian cancer, so as to increase the rate of early diagnosis and to overcome the difficulties of tackling the metastasis of ovarian cancer

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