Overexpression of PRC1 indicates a poor prognosis in ovarian cancer

Overexpression of PRC1 indicates a poor prognosis in ovarian cancer
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PRC1过度表达表明卵巢癌预后不良

DOI:
10.3892/ijo.2020.4959
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发表时间:
2020-03-01
影响因子:
5.2
通讯作者:
Kong, Beihua
Kong, Beihua
中科院分区:
医学2区
文献类型:
--
作者:
Bu, Hualei;Li, Yingwei;Kong, Beihua

文献摘要

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胞质分裂蛋白调节因子-1(PRC1)是一种参与胞质分裂的微管相关因子。最近的研究表明,PRC1的过度表达与多种类型的人类癌症的发生有关。然而,PRC1在卵巢癌中的表达、生物学功能及预后意义尚不清楚。本研究证实高级别浆液性卵巢癌(HGSOC)组织中PRC1mRNA和蛋白表达上调,特别是在无乳腺癌易感基因(BRCA)致病突变的患者中。PRc1过表达导致耐药、肿瘤复发和预后不良。研究结果还表明,Prc1基因敲除降低了卵巢癌细胞的体外增殖、转移和多药耐药性。研究还表明,叉头盒蛋白M1(FOXM1)调控PRC1mRNA和蛋白的表达。双荧光素酶报告实验和挽救实验证实,Prc1是FOXM1的直接关键下游靶点。总体而言,本研究的结果证实了PRC1是HGSOC的主要预后因素,是治疗卵巢癌的一个有前途的治疗生物标志物。
Protein regulator of cytokinesis-1 (PRC1) is a microtubule-associated factor involved in cytokinesis. Recent studies have indicated that PRC1 overexpression is involved in tumorigenesis in multiple types of human cancer. However, the expression, biological functions and the prognostic significance of PRC1 in ovarian cancer have not yet been clarified. In this study, it was confirmed that the PRC1 mRNA and protein expression levels were upregulated in high-grade serous ovarian carcinoma (HGSOC) tissues, particularly in patients without breast cancer susceptibility gene (BRCA) pathogenic mutations. PRC1 overexpression contributed to drug resistance, tumor recurrence and a poor prognosis. The findings also indicated that PRC1 knockdown decreased the proliferation, metastasis and multidrug resistance of ovarian cancer cells in vitro. It was also demonstrated that forkhead box protein M1 (FOXM1) regulated the mRNA and protein expression of PRC1. Dual-luciferase reporter assay and rescue assay confirmed that PRC1 was a direct crucial downstream target of FOXM1. On the whole, the findings of this study confirmed that PRC1 was a major prognostic factor of HGSOC and a promising therapeutic biomarker for the treatment of ovarian cancer.