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miR-582-5p的上调通过靶向Rab27a抑制人结直肠癌中的细胞增殖、细胞周期进程和侵袭。

Upregulation of miR-582-5p inhibits cell proliferation, cell cycle progression and invasion by targeting Rab27a in human colorectal carcinoma.

作者信息

Zhang X, Zhang Y, Yang J, Li S, Chen J

机构信息

Emergency Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.

出版信息

Cancer Gene Ther. 2015 Oct;22(10):475-80. doi: 10.1038/cgt.2015.44. Epub 2015 Sep 18.

Abstract

Colorectal carcinoma (CRC) is known as the most common cancer. MicroRNAs (miRNAs) have been proven to have important roles in human carcinogenesis by regulating various target genes. Recently, the downregulation of miR-582-5p had been demonstrated in CRC. However, its function and the underlying mechanism in CRC remains unknown. In this study, we found that miR-582-5p was frequently downregulated in CRC tissues compared with corresponding noncancerous tissues, as well as in CRC cell lines. Transfection with miR-582-5p mimics significantly inhibited CRC cell proliferation, invasion and arrested cell cycle at the G1/S phase, but promoted cell apoptosis. Further analysis demonstrated that miR-582-5p attenuated the expression of RAS-related GTP-binding protein (Rab27a). Luciferase reporter assay confirmed that Rab27a was a target of miR-582-5p. Mechanism analyses revealed that Rab27a overexpression significantly attenuated the inhibitory effect of miR-582-5p on CRC cell growth, invasion and cell cycle progression. Our data suggest that miR-582-5p may function as a tumor suppressor in the development of CRC by targeting Rab27a, indicating a novel therapeutic strategy for patients with CRC.

摘要

结直肠癌(CRC)是最常见的癌症。微小RNA(miRNA)已被证明通过调节各种靶基因在人类致癌过程中发挥重要作用。最近,已证实在结直肠癌中miR-582-5p表达下调。然而,其在结直肠癌中的功能及潜在机制仍不清楚。在本研究中,我们发现与相应的癌旁组织以及结直肠癌细胞系相比,miR-582-5p在结直肠癌组织中经常下调。用miR-582-5p模拟物转染可显著抑制结直肠癌细胞增殖、侵袭,并使细胞周期停滞在G1/S期,但可促进细胞凋亡。进一步分析表明,miR-582-5p可减弱RAS相关GTP结合蛋白(Rab27a)的表达。荧光素酶报告基因检测证实Rab27a是miR-582-5p的靶标。机制分析显示,Rab27a过表达可显著减弱miR-582-5p对结直肠癌细胞生长、侵袭及细胞周期进程的抑制作用。我们的数据表明,miR-582-5p可能通过靶向Rab27a在结直肠癌发生发展中发挥肿瘤抑制作用,这为结直肠癌患者指明了一种新的治疗策略。

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