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Selenium alters miRNA profile in an intestinal cell line: Evidence that miR-185 regulates expression of GPX2 and SEPSH2

Lookup NU author(s): Anna Maciel Dominguez, Dr Daniel Swan, Professor Dianne Ford, Professor John Hesketh

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Abstract

ScopeIntake of the essential micronutrient selenium (Se) has health implications. This work addressed whether some effects of Se on gene expression are exerted through microRNAs (miRNA). Methods and resultsHuman colon adenocarcinoma cells (Caco-2) were grown in Se-deficient or Se-adequate medium for 72 h. RNA was extracted and subjected to analysis of 737 miRNA using microarray technology. One hundred and forty-five miRNA were found to be expressed in Caco-2 cells. Twelve miRNA showed altered expression after Se depletion: miR-625, miR-492, miR-373*, miR-22, miR-532-5p, miR-106b, miR-30b, miR-185, miR-203, miR1308, miR-28-5p, miR-10b. These changes were validated by quantitative real-time PCR (RT-qPCR). Transcriptomic analysis showed that Se depletion altered expression of 50 genes including selenoproteins GPX1, SELW, GPX3, SEPN1, SELK, SEPSH2 and GPX4. Pathway analysis identified arachidonic acid metabolism, glutathione metabolism, oxidative stress, positive acute phase response proteins and respiration of mitochondria as Se-sensitive pathways. Bioinformatic analysis identified 13 transcripts as targets for the Se-sensitive miRNA; three were predicted to be recognised by miR-185. Silencing of miR-185 increased GPX2 and SEPSH2 expression. ConclusionsWe propose that miR-185 plays a role in up-regulation of GPX2 and SEPHS2 expression. In the case of SEPHS2 this may contribute to maintaining selenoprotein synthesis. The data indicate that micronutrient supply can regulate the cell miRNA expression profile.

Publication metadata

Author(s): Maciel-Dominguez A, Swan D, Ford D, Hesketh J

Publication type: Article

Publication status: Published

Journal: Molecular Nutrition & Food Research

Year: 2013

Volume: 57

Issue: 12

Pages: 2195-2205

Print publication date: 12/08/2013

ISSN (print): 1613-4125

ISSN (electronic): 1613-4133

Publisher: Wiley - VCH Verlag GmbH & Co. KGaA

URL: http://dx.doi.org/10.1002/mnfr.201300168

DOI: 10.1002/mnfr.201300168

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