title: miRNA expression in human intestinal Caco-2 cells is comparably regulated by cis- and trans-fatty acids.
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.
authors.affiliation: Department of Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Solveigh
authors.initials: S
authors.lastname: Köpke
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buhrke
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lampen
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D018938:Caco-2 Cells; D005463:Fluoroacetates / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008042:Linolenic Acids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D044242:Trans Fatty Acids / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C000606775:BCL2L11 protein, human; C481505:BCL2L15 protein, human; D000072224:Bcl-2-Like Protein 11; D005463:Fluoroacetates; D008042:Linolenic Acids; C542542:MIRN146 microRNA, human; C576078:MIRN325 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D044242:Trans Fatty Acids; D051020:bcl-X Protein; C004934:eleostearic acid; C500395:trifluoroacetyl chloride