Dietary Manipulation of Oncogenic MicroRNA Expression in Human Rectal Mucosa: A Randomized Trial
Dietary Manipulation of Oncogenic MicroRNA Expression in Human Rectal Mucosa: A Randomized Trial
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DOI：
10.1158/1940-6207.capr-14-0053
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发表时间：
2014-08-01
影响因子：
3.3
通讯作者：
Le Leu, Richard K.
中科院分区：
文献类型：
--
作者：
Humphreys, Karen J.;Conlon, Michael A.;Le Leu, Richard K.
高红肉（HRM）摄入量与结直肠癌风险增加有关，而抗性淀粉可能具有保护作用。抗性淀粉发酵产生丁酸，这可以改变体外结直肠癌细胞中的microRNA（miRNA）水平;红肉和抗性淀粉对体内miRNA表达的影响尚不清楚。本研究检测了HRM饮食是否改变了健康志愿者直肠粘膜组织中的miRNA表达，以及补充丁酰化抗性淀粉（HRM + HAMSB）是否改变了这种反应。在一项随机交叉设计中，23名志愿者进行了4次为期4周的饮食干预; HRM饮食（300 g/天瘦红肉）和HRM + HAMSB饮食（HRM含40 g/天丁酰化高直链玉米淀粉），之前是进入饮食，并通过洗脱分开。粪便丁酸盐随着HRM + HAMSB饮食而增加。在HRM饮食的直肠粘膜中，致癌成熟miRNA（包括miR17 - 92簇miRNA和miR21）的水平增加，而HRM + HAMSB饮食使miR17 - 92 miRNA恢复至基线水平，但miR21未恢复至基线水平。HRM饮食中升高的miR17 - 92和miR21对应于细胞增殖增加，以及miR17 - 92靶基因转录物水平降低，包括CDKN1A。致癌miR17 - 92簇受增加或降低结直肠癌风险的饮食因素的差异调节，这可能至少部分解释了HRM和抗性淀粉各自的风险特征。这些研究结果支持增加抗性淀粉的消耗作为降低与HRM饮食相关的风险的一种手段。（C）2014年AACR。
High red meat (HRM) intake is associated with increased colorectal cancer risk, while resistant starch is probably protective. Resistant starch fermentation produces butyrate, which can alter microRNA (miRNA) levels in colorectal cancer cells in vitro; effects of red meat and resistant starch on miRNA expression in vivo were unknown. This study examined whether a HRM diet altered miRNA expression in rectal mucosa tissue of healthy volunteers, and if supplementation with butyrylated resistant starch (HRM+HAMSB) modified this response. In a randomized cross-over design, 23 volunteers undertook four 4-week dietary interventions; an HRM diet (300 g/day lean red meat) and an HRM+HAMSB diet (HRM with 40 g/day butyrylated high amylose maize starch), preceded by an entry diet and separated by a washout. Fecal butyrate increased with the HRM+HAMSB diet. Levels of oncogenic mature miRNAs, including miR17-92 cluster miRNAs and miR21, increased in the rectal mucosa with the HRM diet, whereas the HRM+HAMSB diet restored miR17-92 miRNAs, but not miR21, to baseline levels. Elevated miR17-92 and miR21 in the HRM diet corresponded with increased cell proliferation, and a decrease in miR17-92 target gene transcript levels, including CDKN1A. The oncogenic miR17-92 cluster is differentially regulated by dietary factors that increase or decrease risk for colorectal cancer, and this may explain, at least in part, the respective risk profiles of HRM and resistant starch. These findings support increased resistant starch consumption as a means of reducing risk associated with an HRM diet. (C)2014 AACR.