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RPRD1B promotes tumor growth by accelerating the cell cycle in endometrial cancer

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RPRD1B, the regulation of nuclear pre-mRNA domain containing 1B gene, functions as a cell cycle manipulator and has been found overexpressed in a small panel of endometrial cancer types. In the present study, we investigated the roles of RPRD1B in endometrial cancer using various in vitro and in vivo experiments. According to our results, RPRD1B mRNA was significantly upregulated in endometrial cancer tissues (P=0.0012). RPRD1B overexpression was correlated with tumor stage (P=0.0004), histology type (P=0.0146) and depth of myometrial invasion (P=0.024). In vitro, RPRD1B promoted cellular proliferation (P=0.032 for MTT assay and P=0.018 for colony formation assay), and accelerated the cell cycle (P=0.007) by upregulating cyclin D1, CDK4 and CDK6, while knockdown of RPRD1B suppressed cellular proliferation (P=0.02 for MTT assay and P=0.031 for colony formation assay), and led to G1 phase arrest (P=0.025) through downregulating cyclin D1, CDK4 and CDK6. Consistently, in the nude mice model, RPRD1B overexpression significantly accelerated the tumor xenograft growth (P=0.0012), accompanied by elevated Ki-67 and cyclin D1. In addition, we demonstrated that downregulating RPRD1B could sensitize Ishikawa cells to Raloxifene (P=0.01). In summary, we demonstrated that RPRD1B was frequently overexpressed in human endometrial cancer. Both in vitro and in vivo, over-abundant RPRD1B could promote tumor growth and accelerate cellular cell cycle. In addition, knockdown of RPRD1B also increased cell sensitivity to Raloxifene, making RPRD1B a potent therapeutic target for endometrial cancer, particularly in patients with resistance to the selective ER modulators.
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Document Type: Research Article

Affiliations: 1: Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Wuxi, Jiangsu 214062, P.R. China 2: Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiaotong University, Shanghai 200030, P.R. China 3: Department of Radiation Oncology, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China 4: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China

Publication date: March 1, 2014

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