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上调 miR-24-1-5p 的表达参与了黑树莓花色苷对结直肠癌的化学预防作用。

Up-regulation of miR-24-1-5p is involved in the chemoprevention of colorectal cancer by black raspberry anthocyanins.

机构信息

College of Life Science, Liaoning University, Shenyang 110036, People's Republic of China.

Department of Pharmacology, Liaoning University of Traditional Chinese Medicine, Shenyang 110036, People's Republic of China.

出版信息

Br J Nutr. 2019 Sep 14;122(5):518-526. doi: 10.1017/S0007114518003136. Epub 2018 Dec 17.

Abstract

As important epigenetic regulators, microRNA regulate protein expression by triggering the degradation of target mRNA and/or by inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including colorectal cancer. In this study, microRNA-array differential analysis revealed strongly enhanced expression of miR-24-1-5p in the colon tissue of azoxymethane/dextran sulphate sodium-induced mice that were fed with black raspberry anthocyanins for 9 weeks. Overexpression of miR-24-1-5p in human colorectal cancer cells significantly repressed β-catenin expression, and simultaneously decreased cell proliferation, migration and survival. Furthermore, miR-24-1-5p could target β-catenin and trigger a negative regulatory loop for β-catenin and its downstream target genes. β-Catenin signalling is vital to the formation and progression of human colorectal cancer. The current findings therefore identified miR-24-1-5p as a potent regulator of β-catenin, and this may provide a novel chemopreventive and therapeutic strategy for β-catenin signalling-driven colorectal cancer.

摘要

作为重要的表观遗传调控因子,microRNA 通过触发靶 mRNA 的降解和/或抑制其翻译来调节蛋白质表达。miRNA 表达失调已在包括结直肠癌在内的几种癌症中报道。在这项研究中,microRNA 芯片差异分析显示,在喂食黑莓花青素 9 周的氧化偶氮甲烷/葡聚糖硫酸钠诱导的小鼠结肠组织中,miR-24-1-5p 的表达明显增强。miR-24-1-5p 在人结直肠癌细胞中的过表达显著抑制β-catenin 的表达,并同时降低细胞增殖、迁移和存活。此外,miR-24-1-5p 可以靶向β-catenin 并触发β-catenin 及其下游靶基因的负反馈调节环。β-catenin 信号对于人类结直肠癌的形成和进展至关重要。因此,目前的研究结果确定 miR-24-1-5p 是β-catenin 的有效调节因子,这可能为β-catenin 信号驱动的结直肠癌提供一种新的化学预防和治疗策略。

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