Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma.

Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma.
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口腔鳞状细胞癌中胞质分裂1蛋白调节剂对增殖和细胞周期的调节

DOI:
10.1038/s41419-018-0618-6
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发表时间:
2018-05-01
影响因子:
9
通讯作者:
Zhou H
Zhou H
中科院分区:
生物学1区
文献类型:
--
作者:
Wu F;Shi X;Zhang R;Tian Y;Wang X;Wei C;Li D;Li X;Kong X;Liu Y;Guo W;Guo Y;Zhou H

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细胞分裂1蛋白调节因子(PRC1)是一种微管相关蛋白,已成为增殖和凋亡的关键调节因子,主要作用于许多肿瘤。然而,其在口腔鳞状细胞癌(OSCC)中的作用尚不清楚。为了确定PRC1在OSCC中的作用,本研究对95份口腔临床样本(54份OSCC, 24份口腔白斑[OLK], 17份正常口腔黏膜)和7株口腔细胞系(6株OSCC和1株正常口腔细胞系)进行了体内和体外的一系列分子和基因组分析。我们提供的证据表明,在OLK中,PRC1的表达与上皮异常增生程度密切相关(n= 24) (p<0.001),在OSCC中,PRC1的表达与分化差、肿瘤体积大、淋巴结转移、临床分期高密切相关(n= 54) (p<0.05),说明PRC1在OSCC中对肿瘤进展有促进作用。同时,我们观察到PRC1敲低在OSCC细胞系中引起G2/M期阻滞(p<0.05),抑制细胞体外增殖(p<0.05)和体内肿瘤生长(p<0.001)。此外,PRC1对OSCC细胞增殖和细胞周期转变的调控作用是由p53介导的。发现p53/PRC1/EGFR信号通路与OSCC的肿瘤进展有关。根据我们的数据,我们证明PRC1是调节增殖和细胞周期的关键因素,指出PRC1靶向治疗OSCC的潜在益处。
Protein regulator of cytokinesis 1 (PRC1), a microtubule-associated protein, has emerged as a critical regulator of proliferation and apoptosis, acting predominantly in numerous tumors. However, its function in oral squamous cell carcinoma (OSCC) is still unknown. To establish the roles of PRC1 in OSCC, 95 oral clinical samples (54 OSCC, 24 oral leukoplakia [OLK], and 17 normal oral mucosa) and seven oral cell lines (6 OSCC and 1 normal oral cell lines) were analyzed using a series of molecular and genomic assays both in vivo and in vitro were conducted in this study. Herein, we provide evidence demonstrating that expression of PRC1 closely correlates with the degree of epithelial dysplasia in OLK (n= 24) (p<0.001), and the poor differentiation, large tumor volume, lymph node metastasis, and high-clinical stage in OSCC (n= 54) (p<0.05), illustrating that PRC1 has a promotive influence on tumor progression in OSCC. Simultaneously, we observed that PRC1 knockdown in OSCC cell lines caused G2/M phase arrest (p<0.05), inhibited cell proliferation in vitro (p<0.05) and tumor growth in vivo (p<0.001). Furthermore, the effects of PRC1 on the regulation of proliferation and cell cycle transition in OSCC samples were mediated by p53. The p53/PRC1/EGFR signaling pathway was found to be implicated in the tumor progression of OSCC. Based on our data, we demonstrate that PRC1 is a key factor in regulating proliferation and the cell cycle, pointing to the potential benefits of PRC1-targeted therapies for OSCC.
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发表时间: 2012-01
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