n-3 Polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon
n-3 Polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon
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DOI：
10.1093/carcin/bgp245
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发表时间：
2009-12-01
期刊：
影响因子：
4.7
通讯作者：
Chapkin, Robert S.
中科院分区：
文献类型：
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作者：
Davidson, Laurie A.;Wang, Naisyin;Chapkin, Robert S.
我们假设，饮食对肠道非编码RNA[microRNA(MiRNA)]表达的调节可能有助于营养生物活性物质(鱼油和果胶)的化学保护作用。为了充分了解这些制剂对miRNAs表达的影响，SD大鼠被喂以含有玉米油或鱼油和果胶或纤维素的饲料，并注射偶氮甲烷(AOM，一种结肠特异性致癌物质)或生理盐水(对照组)。使用miRNA特异性引物和Taq Man(TM)探针进行实时定量聚合酶链式反应，以定量研究对结肠黏膜miRNA表达的影响。从检测的368个成熟miRNA中，在癌症进展的早期阶段(注射AOM后10周)，let-7d、miR-15b、miR-107、miR-191和miR-324-5p显著受饮食和致癌物交互作用的影响(P<；0.05)。总体而言，喂食鱼油的动物表现出差异表达的miRNAs数量最少(AOM与生理盐水处理相比)。在肿瘤分期方面(注射AOM后34周)，与注射生理盐水的正常黏膜相比，腺癌中46个miRNAs表达异常。在27个在肿瘤中表达水平较高(P<；0.05)的miRNAs中，miR-34a、132、223和224的过度表达是>；10倍。相反，在腺癌中miR-192、194、215和375的表达水平显著降低(0.32倍)。这些结果首次证明了大鼠AOM模型的实用性和鱼油在保护结肠免受致癌物诱导的miRNA失调中的新作用。
We have hypothesized that dietary modulation of intestinal non-coding RNA [microRNA (miRNA)] expression may contribute to the chemoprotective effects of nutritional bioactives (fish oil and pectin). To fully understand the effects of these agents on the expression of miRNAs, Sprague-Dawley rats were fed diets containing corn oil or fish oil with pectin or cellulose and injected with azoxymethane (AOM, a colon-specific carcinogen) or saline (control). Real-time polymerase chain reaction using miRNA-specific primers and Taq Man (TM) probes was carried out to quantify effects on miRNA expression in colonic mucosa. From 368 mature miRNAs assayed, at an early stage of cancer progression (10 week post AOM injection), let-7d, miR-15b, miR-107, miR-191 and miR-324-5p were significantly (P < 0.05) affected by diet x carcinogen interactions. Overall, fish oil fed animals exhibited the smallest number of differentially expressed miRNAs (AOM versus saline treatment). With respect to the tumor stage (34 week post AOM injection), 46 miRNAs were dysregulated in adenocarcinomas compared with normal mucosa from saline-injected animals. Of the 27 miRNAs expressed at higher (P < 0.05) levels in tumors, miR-34a, 132, 223 and 224 were overexpressed at > 10-fold. In contrast, the expression levels of miR-192, 194, 215 and 375 were dramatically reduced (< 0.32-fold) in adenocarcinomas. These results demonstrate for the first time the utility of the rat AOM model and the novel role of fish oil in protecting the colon from carcinogen-induced miRNA dysregulation.