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

Abstract

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.

• Authors: Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Bart Lagerwaard, Seamus Kelly, D Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 56 Issue 9 Pg. 2104-2111 (09 2017) ISSN: 1098-2744 [Electronic] United States
• PMID: 28418082 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The Authors. Molecular Carcinogenesis Published by wiley periodicals, Inc.

Chemical References

• Glucans
• MIRN32 microRNA, human
• MicroRNAs
• Starch
• polydextrose

Topics

• Adult
• Aged
• Colon (drug effects, metabolism)
• Dietary Supplements
• Digestion
• Double-Blind Method
• Female
• Glucans (pharmacology)
• Humans
• Intestinal Mucosa (drug effects)
• Male
• MicroRNAs (biosynthesis)
• Middle Aged
• Polymerase Chain Reaction (methods)
• Rectum (drug effects, metabolism)
• Starch (pharmacology)