The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer.
The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer.
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DOI：
10.1371/journal.pone.0016221
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发表时间：
2011-01-20
期刊：
影响因子：
3.7
通讯作者：
Chang EB
中科院分区：
文献类型：
--
作者：
Hu S;Dong TS;Dalal SR;Wu F;Bissonnette M;Kwon JH;Chang EB
结肠微生物区系发酵未被吸收的膳食纤维以产生大量的短链脂肪酸(SCFA)，这些脂肪酸通过大量的代谢、营养和化学预防作用而造福于宿主。SCFA丁酸酯的化学预防作用部分是通过诱导p21基因表达来实现的。在本研究中，我们评估了microRNA(MiRNA)在丁酸盐诱导p21表达中的作用。用基因芯片和定量聚合酶链式反应分析miRNAs在HCT-116细胞和人散发性结肠癌中的表达谱。通过3‘非编码区荧光素酶报告实验和特异性miRNA模拟物的转染，检测miR-106b对p21基因表达的调节。丁酸盐改变了HCT-116细胞中44个miRNAs的表达，其中许多miRNAs在结肠癌组织中异常表达。MiR-106b家族成员在前者减少，在后者增加。用miR-106b模拟物抑制丁酸诱导的p21蛋白表达。在HCT-116细胞中表达的突变的p213‘UTR报告结构证实了直接的miR-106b靶向。丁酸可抑制HCT-116细胞的增殖，加入miR-106b模拟物可逆转该作用。我们得出结论，微生物来源的单链脂肪酸通过调节miRNAs来调节参与肠道内稳态和致癌的宿主基因的表达。
Colonic microbiota ferment non-absorbed dietary fiber to produce prodigious amounts of short chain fatty acids (SCFAs) that benefit the host through a myriad of metabolic, trophic, and chemopreventative effects. The chemopreventative effects of the SCFA butyrate are, in part, mediated through induction of p21 gene expression. In this study, we assessed the role of microRNA(miRNA) in butyrate's induction of p21 expression. The expression profiles of miRNAs in HCT-116 cells and in human sporadic colon cancers were assessed by microarray and quantitative PCR. Regulation of p21 gene expression by miR-106b was assessed by 3′ UTR luciferase reporter assays and transfection of specific miRNA mimics. Butyrate changed the expression of 44 miRNAs in HCT-116 cells, many of which were aberrantly expressed in colon cancer tissues. Members of the miR-106b family were decreased in the former and increased in the latter. Butyrate-induced p21 protein expression was dampened by treatment with a miR-106b mimic. Mutated p21 3′UTR-reporter constructs expressed in HCT-116 cells confirmed direct miR-106b targeting. Butyrate decreased HCT-116 proliferation, an effect reversed with the addition of the miR-106b mimic. We conclude that microbe-derived SCFAs regulate host gene expression involved in intestinal homeostasis as well as carcinogenesis through modulation of miRNAs.
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影响因子：
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