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miRNA Expression in Human Intestinal Caco-2 Cells is Comparably Regulated by cis- and trans-Fatty Acids

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Lipids

Abstract

Trans-fatty acids are unsaturated fatty acids with at least one double bond in trans configuration. While their role in the development of coronary heart disease is broadly accepted, a potential impact of these fatty acids on colon carcinogenesis is still under discussion. MiRNAs are small non-coding RNAs that regulate the gene expression at a post-transcriptional level by inhibiting the translation of target mRNAs. We investigated the effect of 16 different C 18 fatty acid isomers on the expression of 84 cancer-related miRNAs in the human colorectal adenocarcinoma cell line Caco-2 by using a qRT-PCR array. 66 of these 84 miRNAs were deregulated by at least one fatty acid, however, there was no trans-specific impact on miRNA expression as the corresponding cis isomer of a given fatty acid generally had comparable effects on the miRNA expression profile. The most pronounced effects were observed for hsa-miR-146a-5p, which was upregulated by four of the 16 investigated fatty acids, and hsa-miR-32-5p, which was strongly downregulated by five fatty acids. As hsa-miR-32-5p was described to target genes being involved in the regulation of apoptosis, the effect of α-eleostearic acid on the expression of the apoptosis-associated genes BCL2L11, BCL-2, and BCL-XL was examined. The qPCR results indicate that fatty acid-mediated downregulation of hsa-miR-32-5p is accompanied by a downregulation of BCL-2 and BCL2L11 mRNA whereas BCL-XL was shown to be simultaneously upregulated. In conclusion, our data indicate that several fatty acids are able to regulate miRNA expression of human colon cancer cells. However, no trans-specific regulation was observed.

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Abbreviations

Bcl-2:

B-Cell lymphoma 2

BCL2L11:

Bcl-2-like protein 11 (bim)

BCL-XL:

B-cell lymphoma-extra large

BSA:

Bovine serum albumin

CHD:

Coronary heart disease

cDNA:

Complementary DNA

CRC:

Colorectal cancer

CTB:

Cell titer blue™

DMEM:

Dulbecco’s modified eagle medium

DMSO:

Dimethylsulfoxide

FCS:

Fetal calf serum

ITS:

Insulin-transferrin-selenium supplement

miRNA:

MicroRNA

mRNA:

Messenger RNA

MMP16:

Matrix metalloprotease 16

nt:

Nucleotides

PTEN:

Phosphatase and tensin homologue

qRT-PCR:

Quantitative real time PCR

SCFA:

Short chain fatty acid

snRNA:

Small nuclear RNA

snoRNA:

Small nucleolar RNA

SNP:

Single nucleotide polymorphism

TFA:

Trans fatty acid

wt:

Wild type

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Acknowledgments

S. K. has received a Grant from the Arthur and Aenne Feindt Foundation. We thank Gunnar Quer for technical assistance. This work was funded by the Federal Institute for Risk Assessment (Project no. 1322-474).

Conflicts of interest

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany

    Solveigh Köpke, Thorsten Buhrke & Alfonso Lampen

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  1. Solveigh Köpke
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  2. Thorsten Buhrke
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  3. Alfonso Lampen
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Correspondence to Thorsten Buhrke.

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Köpke, S., Buhrke, T. & Lampen, A. miRNA Expression in Human Intestinal Caco-2 Cells is Comparably Regulated by cis- and trans-Fatty Acids. Lipids 50, 227–239 (2015). https://doi.org/10.1007/s11745-015-3988-x

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  • DOI: https://doi.org/10.1007/s11745-015-3988-x

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