Knockdown of ribosomal protein S6 suppresses proliferation, migration, and invasion in epithelial ovarian cancer
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RESEARCH
Open Access
Knockdown of ribosomal protein S6 suppresses proliferation, migration, and invasion in epithelial ovarian cancer Xueqing Yang1,2, Luxi Xu1,2, Yu-e Yang1,2, Chang Xiong1,2, Jinjin Yu2, Yuan Wang2* and Yaying Lin2*
Abstract Background: Ovarian cancer typically is diagnosed late because insensitivity and lack of specificity of current biomarkers prior to its clinical detection. Ribosomal protein S6 (RPS6) is a ribosomal protein involved in the ribosomal 40S subunit, but its biological role in epithelial ovarian cancer (EOC) is still unknown. Results: RPS6 was elevated in EOC compared to normal ovarian tissues and adenomas. Higher expression of RPS6 predicted worse prognosis in EOC. The level of RPS6 was correlated with clinical stage, histological type and pathological grade. Knockdown of RPS6 reduced the proliferation of ovarian cancer cell lines SKOV-3 and HO8910, and inhibit the migration and invasion ability. It revealed that cells arrested at G0G1 phase after knockdown of RPS6, and the expressions of CyclinD1, Cyclin E, CDK2, CDK4, CDK6 and pRb were also reduced. Conclusions: RPS6 is involved in EOC and knockdown of RPS6 could inhibit the proliferation, invasion and migration ability of EOC in vitro by inducing G0/G1 phase arrest. RPS6 is expected to be a novel biomarker and molecular target to the EOC. Keywords: Ribosomal protein S6 (RPS6), Epithelial ovarian cancer (EOC), G0G1 arrest, Cell proliferation, Invasion, Migration
Background Ovarian cancer is the seventh most commonly diagnosed cancer and the fifth leading cause of cancer-related death among women [1, 2]. A major factor implicated in the high mortality rates from ovarian cancer is that the disease has frequently reached an advanced stage at primary diagnosis [3], as there are no specific clinical symptoms in the early stages. Besides, late detection in part is related to findings since risk-reducing surgeries in BRCA mutation carriers: some of the cancers diagnosed as ovarian cancer may actually arise in the fimbria of the Fallopian Tubes, thus rarely being diagnosed in stage I [4, 5]. Consequently, 70% of patients have advanced disease at primary diagnosis, for which * Correspondence: [email protected]; [email protected] 2 Department of Obstetrics and Gynecology, Affiliated Hospital of Jiangnan University, Wuxi 214000, People’s Republic of China Full list of author information is available at the end of the article
the 5-year survival rate is approximately 29%, compared with 92% for early-stage disease [6]. In eukaryotes, mature ribosomes (80S) contain four RNAs and roughly 80 proteins, which together make up the 60S large and 40S small ribosomal subunits [7]. The interaction between mRNA and the small 40S subunit is a key process in protein synthesis. Ribosomal proteins also have other roles, including participating in DNA repair, and regulating cell proliferation, apoptosis, and differentiation [8]. RPS6 is an important protein constituent of the 40S small subunit, located in the mRNA binding site of cytosolic ri
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