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miR-647在抑制人类胃癌中的作用。

Role of miR-647 in human gastric cancer suppression.

作者信息

Cao Wenlong, Wei Weiyuan, Zhan Zexu, Xie Dongyi, Xie Yubo, Xiao Qiang

机构信息

Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

Department of Anaesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

出版信息

Oncol Rep. 2017 Mar;37(3):1401-1411. doi: 10.3892/or.2017.5383. Epub 2017 Jan 17.

Abstract

MicroRNAs (miRNAs) regulate various oncogenes concomitantly, resulting in tumor suppression. They regulate proliferation and migration pathways in tumor development, suggesting a potential therapeutic role. In the present study, we found that miR-647 was markedly downregulated in gastric cancer (GC), and was significantly correlated with reduced tumor size and metastasis. In addition, miR-647 was also reduced in GC cell lines. Furthermore, overexpression of miR-647 in the GC cell lines inhibited cell proliferation, promoted cell cycle arrest at the G0/G1 phase and induced cell apoptosis. miR-647 also significantly inhibited tumor growth in vivo. Notably, we found that miR-647 overexpression suppressed the migration and invasion of the cancer cells, particularly liver metastasis in nude mice. miR-647 also reduced the expression levels of genes associated with proliferation and metastasis in tumors, including ANK2, FAK, MMP2, MMP12, CD44 and SNAIL1. Overall, our findings demonstrated that miR-647 exerts powerful antitumorigenic effects in vitro and in vivo, and may represent a promising therapeutic agent against GC.

摘要

微小RNA(miRNA)可同时调控多种癌基因,从而发挥肿瘤抑制作用。它们在肿瘤发展过程中调节增殖和迁移途径,提示了其潜在的治疗作用。在本研究中,我们发现miR-647在胃癌(GC)中显著下调,且与肿瘤大小减小和转移显著相关。此外,miR-647在GC细胞系中也减少。进一步研究发现,在GC细胞系中过表达miR-647可抑制细胞增殖,促进细胞周期阻滞于G0/G1期并诱导细胞凋亡。miR-647在体内也显著抑制肿瘤生长。值得注意的是,我们发现miR-647过表达可抑制癌细胞的迁移和侵袭,特别是在裸鼠中的肝转移。miR-647还降低了肿瘤中与增殖和转移相关基因的表达水平,包括ANK2、FAK、MMP2、MMP12、CD44和SNAIL1。总体而言,我们的研究结果表明,miR-647在体外和体内均发挥强大的抗肿瘤作用,可能是一种有前景的抗GC治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d89/5364874/f785ed752007/OR-37-03-1401-g00.jpg

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