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微小RNA-592抑制叉头框蛋白O3(FOXO3)的表达并促进前列腺癌细胞的增殖。

MiR-592 represses FOXO3 expression and promotes the proliferation of prostate cancer cells.

作者信息

Lv Zhonghua, Rao Pinlang, Li Wenlin

机构信息

Department of Urology, Shandong Jining First People's Hospital Jining 272029, Shandong Province, People's Republic of China.

Department of Urology, The Second Hospital of Jiangxi Province Nanchang City Nanchang 333000, Jiang Xi Province, People's Republic of China.

出版信息

Int J Clin Exp Med. 2015 Sep 15;8(9):15246-53. eCollection 2015.

Abstract

Prostate cancer (PC) is a serious health problem all over the world. Cell proliferation plays a major role in the tumorigenesis of PC. It is reported that microRNAs (miRNAs) played crucial roles in the regulation of cell proliferation. However, the underlying mechanism of miRNAs in PC has not been intensively investigated. In the present study, the effect of miR-592 on the cell proliferation of PC was investigated. The results showed that miR-592 was significantly upregulated in PC cell and PC tissues. To investigate the biological roles of miR-592, we induced either the up- or downregulation of miR-592 expression by transfecting DU145 PC cells with miR-592 mimics or miR-592 inhibitor. Our results demonstrated that the upregulation of miR-592promoted cell growth, while miR-592 inhibitor showed the opposite effect. Further experiment revealed that miR-592 repressed the expression of FOXO3 by directly targeting the 3'UTR of the FOXO3 transcript, which resulted in upregulating of the expression of cyclin D1 and downregulating of the expression of p21. In sum, our data indicated a novel aspect of the miR-592 in the molecular etiology of PC.

摘要

前列腺癌(PC)是全球范围内一个严重的健康问题。细胞增殖在PC的肿瘤发生过程中起主要作用。据报道,微小RNA(miRNA)在细胞增殖的调控中发挥关键作用。然而,miRNA在PC中的潜在机制尚未得到深入研究。在本研究中,我们研究了miR-592对PC细胞增殖的影响。结果显示,miR-592在PC细胞和PC组织中显著上调。为了研究miR-592的生物学作用,我们通过用miR-592模拟物或miR-592抑制剂转染DU145 PC细胞来诱导miR-592表达的上调或下调。我们的结果表明,miR-592的上调促进细胞生长,而miR-592抑制剂则显示出相反的效果。进一步的实验表明,miR-592通过直接靶向FOXO3转录本的3'UTR来抑制FOXO3的表达,从而导致细胞周期蛋白D1表达上调和p21表达下调。总之,我们的数据揭示了miR-592在PC分子病因学中的一个新方面。

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