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PTBP1通过调节结肠癌中的细胞凋亡和细胞周期来促进肿瘤发生。

PTBP1 promotes tumorigenesis by regulating apoptosis and cell cycle in colon cancer.

作者信息

Li Xiaona, Han Fei, Liu Wenbin, Shi Xiaoyan

机构信息

Xinxiang Second People's Hospital, Department of Pharmacy, Xinxiang, PR China.

Army Medical University, College of Preventive Medicine, Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, Chongqing, China.

出版信息

Bull Cancer. 2018 Dec;105(12):1193-1201. doi: 10.1016/j.bulcan.2018.08.013. Epub 2018 Oct 8.

Abstract

Increased expression of polypyrimidine tract-binding protein 1 (PTBP1) has been observed in human ovarian tumors, glioblastomas, and breast cancer, but its biological roles in tumorigenesis is not fully clear. In the present research, we investigated the biological role of PTBP1 in colon cancer. We found that PTBP1 was overexpressed both in colon cancer cell lines and tissues. Tissue microarray analysis (TMA) indicated that low PTBP1 expression predicted a favorable overall survival for colon cancer patients. Using small interfering RNA technology, we found that down-regulation of PTBP1 significantly inhibited colon cancer cell growth/proliferation, and induced cell cycle arrest as well as apoptosis in vitro. Western blot analysis showed that siRNA PTBP1 could up-regulate the expression of cytoC, p53 and Bax as well as down-regulated p85, p-AKT, cyclinD1, CDK4 and Bcl2 compared to the control. Furthermore, Caspase-3 and PARP1 were activated when PTBP1 is knockdown. This study implies that PTBP1 plays an important role in tumorigenesis of colon cancer.

摘要

在人类卵巢肿瘤、胶质母细胞瘤和乳腺癌中已观察到多嘧啶序列结合蛋白1(PTBP1)的表达增加,但其在肿瘤发生中的生物学作用尚不完全清楚。在本研究中,我们调查了PTBP1在结肠癌中的生物学作用。我们发现PTBP1在结肠癌细胞系和组织中均过度表达。组织芯片分析(TMA)表明,PTBP1低表达预示着结肠癌患者的总生存期良好。使用小干扰RNA技术,我们发现PTBP1的下调显著抑制结肠癌细胞的生长/增殖,并在体外诱导细胞周期停滞和凋亡。蛋白质印迹分析表明,与对照组相比,siRNA PTBP1可上调细胞色素C、p53和Bax的表达,并下调p85、p-AKT、细胞周期蛋白D1、细胞周期蛋白依赖性激酶4(CDK4)和Bcl2的表达。此外,当PTBP1被敲低时,半胱天冬酶-3(Caspase-3)和聚(ADP-核糖)聚合酶1(PARP1)被激活。本研究表明,PTBP1在结肠癌的肿瘤发生中起重要作用。

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