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Lookup NU author(s): Dr Fiona MalcomsonORCiD, Dr Naomi Willis, Iain McCallum, Dr Long Xie, Bart Lagerwaard, Seamus Kelly, Professor John Mathers
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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 randomised, double-blind, placebo-controlled dietary intervention. We screened 1,008 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 two-fold 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 three-fold (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 signalling via regulation of TRAF3 expression and consequently NIK stabilisation.
Author(s): Malcomson FC, Willis ND, McCallum I, Xie L, Lagerwaard B, Kelly S, Bradburn M, Belshaw NJ, Johnson IT, Mathers JC
Publication type: Article
Publication status: Published
Journal: Molecular Carcinogenesis
Year: 2017
Volume: 56
Issue: 9
Pages: 2104-2111
Print publication date: 01/09/2017
Online publication date: 18/04/2017
Acceptance date: 17/04/2017
Date deposited: 27/04/2017
ISSN (print): 0899-1987
ISSN (electronic): 1098-2744
Publisher: Wiley
URL: https://doi.org/10.1002/mc.22666
DOI: 10.1002/mc.22666
PubMed id: 28418082
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