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