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微小 RNA-191 靶向 N-脱乙酰基/N-磺基转移酶 1 并促进人胃癌细胞系 MGC803 的细胞生长。

MicroRNA-191 targets N-deacetylase/N-sulfotransferase 1 and promotes cell growth in human gastric carcinoma cell line MGC803.

机构信息

Department of Oncology, Jingzhou Hospital, Tongji Medical College of Huazhong University of Science and Technology, Jingzhou 434020, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2011 Nov;43(11):849-56. doi: 10.1093/abbs/gmr084. Epub 2011 Sep 22.

Abstract

As a family of post-transcriptional regulator of gene expression, the microRNAs (miRNAs) control a wide array of biological processes including cell differentiation, proliferation and apoptosis, and the dysregulation of miRNAs is a hallmark of cancer. Here, we found that the microRNA-191 (miR-191) was at a high-expression level in human gastric adenocarcinoma cell line MGC803 and human gastric cancer tissues. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays showed that miR-191 could promote cell growth and suppress apoptosis of MGC803 cells. The N-deacetylase/N-sulfotransferase 1 (NDST1) was confirmed to be a direct target gene of miR-191 by enhanced green fluorescent protein reporter experiment. The mRNA and protein levels of NDST1 were inversely correlated with miR-191 in MGC803 cells, suggesting the negative regulation of NDST1 by miR-191. Furthermore, NDST1 played an inhibitory role and could suppress MGC803 cell proliferation. Our findings suggested that miR-191 could act as an oncogene in MGC803 cells, and the cellular function was partially due to its negative regulation of NDST1.

摘要

作为基因表达转录后调控因子家族的一员,microRNAs(miRNAs)调控着广泛的生物学过程,包括细胞分化、增殖和凋亡,miRNAs 的失调是癌症的一个标志。在这里,我们发现 microRNA-191(miR-191)在人胃腺癌细胞系 MGC803 和人胃癌组织中呈高表达水平。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和集落形成实验的结果表明,miR-191 可以促进 MGC803 细胞的生长并抑制其凋亡。增强型绿色荧光蛋白报告实验证实 N-脱乙酰基/N-磺基转移酶 1(NDST1)是 miR-191 的直接靶基因。在 MGC803 细胞中,NDST1 的 mRNA 和蛋白水平与 miR-191 呈负相关,提示 miR-191 对 NDST1 的负调控。此外,NDST1 发挥抑制作用并可抑制 MGC803 细胞增殖。我们的研究结果表明,miR-191 可作为 MGC803 细胞中的癌基因发挥作用,其细胞功能部分归因于其对 NDST1 的负调控。

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