Suppr超能文献

共激活因子相关精氨酸甲基转移酶1促进细胞生长,且在人类结直肠癌中是微小RNA-195-5p的作用靶点。

Coactivator-associated arginine methyltransferase 1 promotes cell growth and is targeted by microRNA-195-5p in human colorectal cancer.

作者信息

Zhang Meifeng, Wu Wei, Gao Ming, Zhang Jie, Ding Xinde, Zhu Ronghua, Chen Haiqun, Fei Zhewei

机构信息

Department of General Surgery, Xinhua Hospital, Chongming Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.

出版信息

Tumour Biol. 2017 Mar;39(3):1010428317694305. doi: 10.1177/1010428317694305.

Abstract

The pathogenesis of colorectal cancer remains poorly understood. Here, we show that coactivator-associated arginine methyltransferase 1 is frequently upregulated in colorectal cancer tissues and promotes cell growth in vitro and in vivo. Using bioinformatics-based prediction and luciferase reporter system, we found that coactivator-associated arginine methyltransferase 1 is post-transcriptionally targeted by microRNA-195-5p in colorectal cancer. Ectopic expression of microRNA-195-5p led to the suppression of the coactivator-associated arginine methyltransferase 1 3'-untranslated regions activity and downregulation of the endogenous coactivator-associated arginine methyltransferase 1 protein in colorectal cancer cells. Expression analysis verified that microRNA-195-5p was markedly downregulated in human colorectal cancer tissues, which was negatively correlated with the elevated levels of coactivator-associated arginine methyltransferase 1 protein. Enhanced levels of microRNA-195-5p in colorectal cancer cells resulted in a sharp reduction of cell proliferative and colony-formative capacities in vitro. Remarkably, restoration of coactivator-associated arginine methyltransferase 1 in microRNA-195-5p-transfected colorectal cancer cells partially abrogated the inhibition of cell proliferation and colony formation mediated through microRNA-195-5p. These data confirm that microRNA-195-5p might function as an anti-tumor microRNA in colorectal cancer exerting critical control over coactivator-associated arginine methyltransferase 1 expression. The newly identified microRNA-195-5p/coactivator-associated arginine methyltransferase 1 axis may act as a novel promising therapeutic target for colorectal cancer treatment.

摘要

结直肠癌的发病机制仍未得到充分了解。在此,我们表明共激活因子相关精氨酸甲基转移酶1在结直肠癌组织中经常上调,并在体外和体内促进细胞生长。通过基于生物信息学的预测和荧光素酶报告系统,我们发现共激活因子相关精氨酸甲基转移酶1在结直肠癌中受到微小RNA-195-5p的转录后靶向作用。微小RNA-195-5p的异位表达导致结直肠癌细胞中共激活因子相关精氨酸甲基转移酶1 3'非翻译区活性的抑制以及内源性共激活因子相关精氨酸甲基转移酶1蛋白的下调。表达分析证实,微小RNA-195-5p在人类结直肠癌组织中明显下调,这与共激活因子相关精氨酸甲基转移酶1蛋白水平的升高呈负相关。结直肠癌细胞中微小RNA-195-5p水平的提高导致体外细胞增殖和集落形成能力急剧下降。值得注意的是,在转染了微小RNA-195-5p的结直肠癌细胞中恢复共激活因子相关精氨酸甲基转移酶1的表达,部分消除了通过微小RNA-195-5p介导的对细胞增殖和集落形成的抑制作用。这些数据证实,微小RNA-195-5p可能作为结直肠癌中的一种抗肿瘤微小RNA,对共激活因子相关精氨酸甲基转移酶1的表达发挥关键调控作用。新发现的微小RNA-195-5p/共激活因子相关精氨酸甲基转移酶1轴可能成为结直肠癌治疗的一个新的有前景的治疗靶点。

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验