Non-digestible carbohydrates supplementation increases miR-32 expression in the healthy human colorectal epithelium: A randomized controlled trial.

Non-digestible carbohydrates supplementation increases miR-32 expression in the healthy human colorectal epithelium: A randomized controlled trial.
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不可消化的碳水化合物补充剂在健康的人类大肠上皮中增加了miR-32的表达:一项随机对照试验。

DOI:
10.1002/mc.22666
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发表时间:
2017-09
影响因子:
4.6
通讯作者:
Mathers JC
Mathers JC
中科院分区:
医学2区
文献类型:
--
作者:
Malcomson FC;Willis ND;McCallum I;Xie L;Lagerwaard B;Kelly S;Bradburn DM;Belshaw NJ;Johnson IT;Mathers JC

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结直肠癌(CRC)风险受饮食调节,并且有令人信服的证据表明,较高的非消化性碳水化合物(NDC)摄入量可降低风险。抗性淀粉(RS),一种NDC,积极调节致癌microRNA的表达,这表明这可能是NDC保护CRC的机制。本研究旨在使用来自DISC研究(一项随机、双盲、安慰剂对照饮食干预)的样本,研究补充两种NDC(RS和聚葡萄糖(PD))对肉眼正常人直肠上皮中microRNA表达的影响。我们从分配到双安慰剂组的参与者和补充RS和PD的参与者的合并干预后直肠粘膜样本中筛选了1008个miRNA。与对照组相比,RS + PD组中共有111种miRNAs上调或下调至少两倍。其中,选择了8种用于通过qPCR在个体参与者样品中进行定量,并且倍数变化方向与7种miRNA的阵列一致。miR-133 b的不一致性和7种miRNA观察到的较低倍数变化值可能是因为个体参与者样本的qPCR是比阵列更稳健和灵敏的定量方法。与安慰剂相比,补充RS + PD的参与者的直肠粘膜中miR-32表达增加约3倍(P = 0.033)。miR-32参与调控CRC中失调的细胞增殖等过程。此外,miR-32可能通过调节TRAF 3表达进而影响NIK稳定性来影响非经典NF-κB信号传导。
Colorectal cancer (CRC) risk is modulated by diet and there is convincing evidence of reduced risk with higher non‐digestible carbohydrates (NDCs) consumption. Resistant starch (RS), a NDC, positively modulates the expression of oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs protect against CRC. The present study aimed to investigate the effects of supplementation with two NDCs, RS, and polydextrose (PD), on microRNA expression in the macroscopically‐normal human rectal epithelium using samples from the DISC Study, a randomized, double‐blind, placebo‐controlled dietary intervention. We screened 1008 miRNAs in pooled post‐intervention rectal mucosal samples from participants allocated to the double placebo group and those supplemented with both RS and PD. A total of 111 miRNAs were up‐ or down‐regulated by at least twofold in the RS + PD group compared with the control group. From these, eight were selected for quantification in individual participant samples by qPCR, and fold‐change direction was consistent with the array for seven miRNAs. The inconsistency for miR‐133b and the lower fold‐change values observed for the seven miRNAs is probably because qPCR of individual participant samples is a more robust and sensitive method of quantification than the array. miR‐32 expression was increased by approximately threefold (P = 0.033) in the rectal mucosa of participants supplemented with RS + PD compared with placebo. miR‐32 is involved in the regulation of processes such as cell proliferation that are dysregulated in CRC. Furthermore, miR‐32 may affect non‐canonical NF‐κB signaling via regulation of TRAF3 expression and consequently NIK stabilization.
Warburg效应决定了丁酸酯介导的组蛋白乙酰化和细胞增殖的机制。
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