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Overexpression of YBX1 Promotes Pancreatic Ductal Adenocarcinoma Growth via the GSK3B/Cyclin D1/Cyclin E1 Pathway.
Molecular Therapy - Oncolytics ( IF 5.7 ) Pub Date : 2020-03-29 , DOI: 10.1016/j.omto.2020.03.006
Zhiqiang Liu 1 , Yongfeng Li 2 , Xiaogang Li 1 , Jingyuan Zhao 1 , Shihong Wu 1 , Heshui Wu 1 , Shanmiao Gou 1
Affiliation  

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers due to frequently late diagnosis and futile treatment. It is a crucial necessity to determine the mechanisms of PDAC. Y-box Binding Protein 1 (YBX1), a highly conserved transcription factor, has been previously reported to play a role in various hallmarks of cancer. We show here that YBX1 is significantly overexpressed in PDAC and correlates with poor prognosis and reduced survival. In PDAC cell lines, YBX1 regulated cell-cycle progression, proliferation, and the expression of glycogen synthase kinase 3 beta (GSK3B) and cell-cycle-related proteins cyclin D1 and E1. Dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays established that YBX1 binds to the promoter of GSK3B, suggesting that YBX1 promotes pancreatic cancer cell growth through induction of GSK3B expression. These findings offer important insights into the mechanisms underlying pathologic proliferation in PDAC.



中文翻译:

YBX1的过表达通过GSK3B / Cyclin D1 / Cyclin E1途径促进胰腺导管腺癌的生长。

胰腺导管腺癌(PDAC)由于经常误诊和无效治疗而成为最致命的癌症之一。确定PDAC的机制是至关重要的。Y-box结合蛋白1(YBX1),一种高度保守的转录因子,先前已报道在多种癌症特征中起作用。我们在这里显示,YBX1在PDAC中明显过表达,并且与不良预后和降低的生存率相关。在PDAC细胞系中,YBX1调节细胞周期进程,增殖以及糖原合酶激酶3 beta(GSK3B)和细胞周期相关蛋白cyclin D1和E1的表达。双荧光素酶报告基因和染色质免疫沉淀(ChIP)分析确定YBX1与GSK3B启动子结合,表明YBX1通过诱导GSK3B表达促进胰腺癌细胞的生长。这些发现为PDAC病理增生的潜在机制提供了重要见解。

更新日期:2020-03-29
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