Coffee reduces KRAS expression in Caco-2 human colon carcinoma cells via regulation of miRNAs.
Coffee reduces KRAS expression in Caco-2 human colon carcinoma cells via regulation of miRNAs.
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DOI：
10.3892/ol.2017.6227
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发表时间：
2017-07
期刊：
影响因子：
2.9
通讯作者：
T. Nakayama;M. Funakoshi-Tago;H. Tamura
中科院分区：
文献类型：
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作者：
T. Nakayama;M. Funakoshi-Tago;H. Tamura
以前的流行病学研究表明，适量饮用咖啡与某些类型癌症的风险降低有关，特别是结肠癌。为了阐明这种保护作用的分子基础，研究了咖啡对Caco-2人结肠癌细胞的作用。低浓度的咖啡（<5%）抑制Caco-2细胞的增殖，而不影响细胞活力。咖啡还以剂量依赖性方式降低KRAS原癌基因GT3（KRAS）基因表达;然而，咖啡因、咖啡酸和绿原酸这三种咖啡的主要成分并没有表现出这种作用。增加咖啡豆烘焙的持续时间增加了KRAS表达的减少，这表明负责这种效果的活性成分在烘焙过程中出现。microRNA（miR）分析显示，咖啡诱导了miR-30 c和miR-96的表达，这两种基因都靶向KRAS基因。目前的研究结果表明，每天喝咖啡可能会降低KRAS活性，从而防止结肠癌细胞的恶性生长。
Previous epidemiological studies have demonstrated that moderate coffee consumption is associated with a lower risk of certain types of cancer, particularly colon cancer. To elucidate the molecular basis for this protective action, the effect of coffee on Caco-2 human colon carcinoma cells was investigated. Low concentrations of coffee (<5%) inhibited proliferation of Caco-2 cells without affecting cell viability. Coffee also reduced KRAS proto-oncogene, GTPase (KRAS) gene expression in a dose-dependent manner; however, caffeine, caffeic acid and chlorogenic acid, three major constituents of coffee, did not exhibit this effect. Increasing the duration of coffee bean roasting increased the reduction in KRAS expression, suggesting that the active constituents responsible for this effect emerged during the roasting process. MicroRNA (miR) analysis revealed that coffee induced the expression of miR-30c and miR-96, both of which target the KRAS gene. The results of the present study suggested that daily coffee consumption may reduce KRAS activity, thereby preventing the malignant growth of colon carcinoma cells.