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Obesity and Roux-en-Y gastric bypass drive changes in miR-31 and miR-215 expression in the human rectal mucosa

Lookup NU author(s): Dr Stella Breininger, Laura Sabater, Dr Fiona Malcomson, Sorena Afshar, Professor Jelena Mann, Professor John Mathers

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021, The Author(s).Background/Objectives: Obesity increases colorectal cancer (CRC) risk. However, the effects of weight loss on CRC risk are unclear. Epigenetic mechanisms involving microRNAs that lead to dysregulated gene expression may mediate the effects of obesity and weight loss on CRC risk. We examined the effects of obesity and weight loss following Roux-en-Y gastric bypass (RYGB) on microRNA expression in the human rectal mucosa. Subjects/Methods: We collected rectal mucosal biopsies from obese patients (n = 22) listed for RYGB and age- and sex-matched healthy non-obese Controls (n = 20), at baseline and six months post-surgery. We quantified microRNA expression in rectal mucosal biopsies using Next Generation Sequencing and bioinformatics analysis to investigate the likely functional consequences of these epigenetic changes. Results: Compared with non-obese individuals, obese individuals showed differential expression of 112 microRNAs (p < 0.05). At six-months post-RYGB, when mean body mass had fallen by 27 kg, 60 microRNAs were differentially expressed, compared with baseline (p < 0.05). The expression of 36 microRNAs differed significantly between both i) obese and non-obese individuals and ii) obese individuals pre- and post-RYGB. Quantitative polymerase chain reaction (qPCR) demonstrated that expression of miR-31 and miR-215 was significantly (p < 0.05) higher, 143-fold and 15-fold respectively, in obese than in non-obese individuals. Weight loss, following RYGB, reduced expression of miR-31 and miR-215 to levels comparable with Controls. These differentially expressed microRNAs are implicated in pathways linked with inflammation, obesity and cancer. Conclusion: Our findings show, for the first time, that obesity is associated with dysregulated microRNA expression in the human rectal mucosa. Further, surgically-induced weight loss may normalise microRNA expression in this tissue.


Publication metadata

Author(s): Breininger SP, Sabater L, Malcomson FC, Afshar S, Mann J, Mathers JC

Publication type: Article

Publication status: Published

Journal: International Journal of Obesity

Year: 2021

Pages: epub ahead of print

Online publication date: 29/10/2021

Acceptance date: 15/10/2021

Date deposited: 16/11/2021

ISSN (print): 0307-0565

ISSN (electronic): 1476-5497

Publisher: Springer Nature

URL: https://doi.org/10.1038/s41366-021-01005-y

DOI: 10.1038/s41366-021-01005-y


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