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微小RNA-503通过靶向E2F3抑制结肠癌细胞增殖并诱导其凋亡。

miR-503 inhibits cell proliferation and induces apoptosis in colorectal cancer cells by targeting E2F3.

作者信息

Chang Shun-Wu, Yue Jie, Wang Bao-Chun, Zhang Xue-Li

机构信息

Department of Surgery, Third Clinical Medical College of Southern Medical University Guangzhou 510630, China ; Department of Surgery, People's Hospital of Hainan Province Haikou 570311, China.

Department of Surgery, People's Hospital of Hainan Province Haikou 570311, China.

出版信息

Int J Clin Exp Pathol. 2015 Oct 1;8(10):12853-60. eCollection 2015.

Abstract

OBJECTIVE

Colorectal cancer (CRC) is one of the major healthcare problems worldwide. A lot of miRNAs are aberrantly expressed in CRC and involved in its development and progression. The purpose of this study was to investigate the expression and function of miR-503 in CRC.

METHODS

miR-503 expression was detected in CRC tissues and cell lines by Quantitative real-time PCR. Cell proliferation was assessed by MTT assay. Cell apoptosis and cell cycle distribution were measured by flow cytometry. Moreover, luciferase reporter assay and western blot were performed to determine the potential target of miR-503 in CRC cells.

RESULTS

miR-503 was significantly decreased in CRC tissues and cell lines in comparison with controls. Overexpression of miR-503 in CRC cells remarkably inhibited cell proliferation and induced apoptosis. Furthermore, E2F3 was identified as a direct target of miR-503 in CRC cells and down-regulation of E2F3 had a similar effect as miR-503 overexpression on CRC cells. In addition, the expression of E2F3 was negatively correlated with miR-503 level in CRC tissues.

CONCLUSIONS

miR-503 inhibits cell proliferation and induces apoptosis by directly targeting E2F3 in CRC cells, indicating its potential application in CRC diagnosis and therapy.

摘要

目的

结直肠癌(CRC)是全球主要的医疗保健问题之一。许多微小RNA(miRNA)在CRC中异常表达,并参与其发生和发展。本研究旨在探讨miR-503在CRC中的表达及功能。

方法

采用定量实时聚合酶链反应(Quantitative real-time PCR)检测CRC组织和细胞系中miR-503的表达。通过MTT法评估细胞增殖。采用流式细胞术检测细胞凋亡和细胞周期分布。此外,进行荧光素酶报告基因检测和蛋白质免疫印迹法(western blot)以确定miR-503在CRC细胞中的潜在靶点。

结果

与对照组相比,CRC组织和细胞系中miR-503显著降低。在CRC细胞中过表达miR-503可显著抑制细胞增殖并诱导凋亡。此外,E2F3被鉴定为CRC细胞中miR-503的直接靶点,E2F3的下调对CRC细胞的作用与miR-503过表达相似。此外,CRC组织中E2F3的表达与miR-503水平呈负相关。

结论

miR-503通过直接靶向CRC细胞中的E2F3抑制细胞增殖并诱导凋亡,表明其在CRC诊断和治疗中的潜在应用价值。

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