GTSE1、CDC20、PCNA和MCM6協(xié)同影響肝癌細(xì)胞周期調(diào)控并提示預(yù)后不良

2019年12月，中國醫(yī)學(xué)科學(xué)院；北京協(xié)和醫(yī)學(xué)院北京協(xié)和醫(yī)院肝臟外科；中國醫(yī)學(xué)科學(xué)院；北京協(xié)和醫(yī)學(xué)院醫(yī)學(xué)生物學(xué)研究所樹鼩種質(zhì)資源研究中心；云南省重癥傳染病疫苗研究與開發(fā)重點(diǎn)實(shí)驗(yàn)室；貴州醫(yī)科大學(xué)附屬醫(yī)院；清華大學(xué)自動(dòng)化系生物信息學(xué)學(xué)部合成與系統(tǒng)生物學(xué)中心生物信息學(xué)教育部重點(diǎn)實(shí)驗(yàn)室；清華大學(xué)醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)部；清華-北京生命科學(xué)聯(lián)合中心 (Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China；Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming,Yunnan 650118, China；Department of Hepatobiliary Surgery,   Affiliated Hospital of Guizhou Medical University, No. 28, Guiyi Street, Yunyan District, 550004 Guiyang, China；MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Bioinformatics Division, BNRist,Department of Automation, Tsinghua University, Beijing 100084, China；Department of Basic Medical Science, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University,Beijing 100084, China) Yongchang Zheng老師研究團(tuán)隊(duì)在《Analytical Cellular Pathology》上發(fā)表論文：

“GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer”

“GTSE1、CDC20、PCNA和MCM6協(xié)同影響肝癌細(xì)胞周期調(diào)控并提示預(yù)后不良”

Abstract：

GTSE1 is well correlated with tumor progression; however, little is known regarding its role in liver cancer prognosis. By analyzing the hepatocellular carcinoma (HCC) datasets in GEO and TCGA databases, we showed that high expression of GTSE1 was correlated with advanced pathologic stage and poor prognosis of HCC patients. To investigate underlying molecular mechanism, we generated GTSE1 knockdown HCC cell line and explored the effects of GTSE1 deficiency in cell growth. Between GTSE1 knockdown and wild-type HCC cells, we identified 979 differentially expressed genes (520 downregulated and 459 upregulated genes) in the analysis of microarray-based gene expression profiling. Functional enrichment analysis of DEGs suggested that S phase was dysregulated without GTSE1 expression, which was further verified from flow cytometry analysis. Moreover, three other DEGs: CDC20, PCNA, and MCM6, were also found contributing to GTSE1-related cell cycle arrest and to be associated with poor overall survival of HCC patients. In conclusion, GTSE1, together with CDC20, PCNA, and MCM6, may synergistically promote adverse prognosis in HCC by activating cell cycle. Genes like GTSE1, CDC20, PCNA, and MCM6 may be promising prognostic molecular biomarkers in liver cancer.

摘要：

GTSE1與腫瘤進(jìn)展密切相關(guān);然而，其在肝癌預(yù)后中的作用尚不清楚。通過分析GEO和TCGA數(shù)據(jù)庫中的肝細(xì)胞癌(HCC)數(shù)據(jù)集，我們發(fā)現(xiàn)GTSE1的高表達(dá)與HCC患者的病理分期晚期和預(yù)后不良相關(guān)。為了研究其潛在的分子機(jī)制，我們建立了GTSE1敲低的HCC細(xì)胞株，并探討了GTSE1缺乏對(duì)細(xì)胞生長的影響。在GTSE1敲低和野生型HCC細(xì)胞之間，我們?cè)诨谖㈥嚵械幕虮磉_(dá)譜分析中發(fā)現(xiàn)了979個(gè)差異表達(dá)基因(520個(gè)下調(diào)基因和459個(gè)上調(diào)基因)。DEGs功能富集分析提示S期表達(dá)異常，無GTSE1表達(dá)，流式細(xì)胞術(shù)分析進(jìn)一步證實(shí)了這一點(diǎn)。此外，另外三種deg: CDC20、PCNA和MCM6也被發(fā)現(xiàn)有助于gtse1相關(guān)的細(xì)胞周期阻滯，并與HCC患者的總生存期差相關(guān)。綜上所述，GTSE1與CDC20、PCNA、MCM6可能通過激活細(xì)胞周期協(xié)同促進(jìn)HCC的不良預(yù)后。GTSE1、CDC20、PCNA和MCM6等基因可能是肝癌預(yù)后的有希望的分子生物標(biāo)志物。

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