, Volume 50, Issue 3, pp 227–239 | Cite as

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

  • Solveigh Köpke
  • Thorsten BuhrkeEmail author
  • Alfonso Lampen
Original Article


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.


miRNA trans-fatty acid CRC Colorectal cancer hsa-miR-32 Caco-2 Fatty acid TFA 



B-Cell lymphoma 2


Bcl-2-like protein 11 (bim)


B-cell lymphoma-extra large


Bovine serum albumin


Coronary heart disease


Complementary DNA


Colorectal cancer


Cell titer blue™


Dulbecco’s modified eagle medium




Fetal calf serum


Insulin-transferrin-selenium supplement




Messenger RNA


Matrix metalloprotease 16




Phosphatase and tensin homologue


Quantitative real time PCR


Short chain fatty acid


Small nuclear RNA


Small nucleolar RNA


Single nucleotide polymorphism


Trans fatty acid


Wild type



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.


  1. 1.
    Mozaffarian D, Aro A, Willett WC (2009) Health effects of trans-fatty acids: experimental and observational evidence. Eur J Clin Nutr 63:S5–S21CrossRefPubMedGoogle Scholar
  2. 2.
    Stender S, Dyerberg J (2004) Influence of trans fatty acids on health. Ann Nutr Metab 48:61–66CrossRefPubMedGoogle Scholar
  3. 3.
    Mozaffarian D, Katan MB, Ascherio A, Stampfer MJ, Willett WC (2006) Trans fatty acids and cardiovascular disease. New Engl J Med 354:1601–1613CrossRefPubMedGoogle Scholar
  4. 4.
    Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC (2000) Primary prevention of coronary heart disease in women through diet and lifestyle. New Engl J Med 343:16–22CrossRefPubMedGoogle Scholar
  5. 5.
    Willett WC (1994) Diet and health—what should we eat. Science 264:532–537CrossRefPubMedGoogle Scholar
  6. 6.
    Otite FO, Jacobson MF, Dahmubed A, Mozaffarian D (2013) Trends in trans fatty acids reformulations of US supermarket and brand-name foods from 2007 through 2011. Prev Chronic Dis 10:E85CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Mozaffarian D, Jacobson MF, Greenstein JS (2010) Food reformulations to reduce trans fatty acids. New Engl J Med 362:2037–2039CrossRefPubMedGoogle Scholar
  8. 8.
    Mozaffarian D, Stampfer MJ (2010) Removing industrial trans fat from foods. BMJ 340:c1826CrossRefPubMedGoogle Scholar
  9. 9.
    Angell SY, Silver LD, Goldstein GP, Johnson CM, Deitcher DR, Frieden TR, Bassett MT (2009) Cholesterol control beyond the clinic: New York City’s trans fat restriction. Ann Int Med 151:129–133CrossRefPubMedGoogle Scholar
  10. 10.
    Dhaka V, Gulia N, Ahlawat KS, Khatkar BS (2011) Trans fats-sources, health risks and alternative approach—a review. J Food Sci Technol-Mysore 48:534–541CrossRefGoogle Scholar
  11. 11.
    Leth T, Jensen HG, Mikkelsen AAE, Bysted A (2006) The effect of the regulation on trans fatty acid content in Danish food. Atheroscler Suppl 7:53–56CrossRefPubMedGoogle Scholar
  12. 12.
    Vinikoor LC, Schroeder JC, Millikan RC, Satia JA, Martin CF, Ibrahim J, Galanko JA, Sandler RS (2008) Consumption of trans-fatty acid and its association with colorectal adenomas. Am J Epidemiol 168:289–297CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Vinikoor LC, Millikan RC, Satia JA, Schroeder JC, Martin CF, Ibrahim JG, Sandler RS (2010) Trans-fatty acid consumption and its association with distal colorectal cancer in the North Carolina Colon Cancer Study II. Cancer Causes Control 21:171–180CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Slattery ML, Benson J, Ma KN, Schaffer D, Potter JD (2001) Trans-fatty acids and colon cancer. Nutr Cancer 39:170–175CrossRefPubMedGoogle Scholar
  15. 15.
    Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107:823–826CrossRefPubMedGoogle Scholar
  16. 16.
    Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355CrossRefPubMedGoogle Scholar
  17. 17.
    Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nature Rev Cancer 6:857–866CrossRefGoogle Scholar
  18. 18.
    Lee YS, Dutta A (2006) MicroRNAs: small but potent oncogenes or tumor suppressors. Curr Opin Invest Drugs 7:560–564Google Scholar
  19. 19.
    Zhang B, Pan X, Cobb GP, Anderson TA (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12CrossRefPubMedGoogle Scholar
  20. 20.
    Yao Y, Suo A-L, Li Z-F, Liu L-Y, Tian T, Ni L, Zhang W-G, Nan K-J, Song T-S, Huang C (2009) MicroRNA profiling of human gastric cancer. Mol Med Reports 2:963–970Google Scholar
  21. 21.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebet BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838CrossRefPubMedGoogle Scholar
  22. 22.
    Luo X, Burwinkel B, Tao S, Brenner H (2011) MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiol Biomarkers Prev 20:1272–1286CrossRefPubMedGoogle Scholar
  23. 23.
    Hu S, Dong TS, Dalal SR, Wu F, Bissonnette M, Kwon JH, Chang EB (2011) The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer. PLoS One 6:e16221CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Gocek E, Wang X, Liu X, Liu C-G, Studzinski GP (2011) MicroRNA-32 upregulation by 1,25-dihydroxyvitamin D3 in human myeloid leukemia cells leads to Bim targeting and inhibition of AraC-induced apoptosis. Cancer Res 71:6230–6239CrossRefPubMedGoogle Scholar
  25. 25.
    Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nature Rev Mol Cell Biol 9:47–59CrossRefGoogle Scholar
  26. 26.
    McKelvey W, Greenland S, Chen MJ, Longnecker MP, Frankl HD, Lee ER, Haile RW (1999) A case-control study of colorectal adenomatous polyps and consumption of foods containing partially hydrogenated oils. Cancer Epidemiol Biomarkers Prev 8:519–524PubMedGoogle Scholar
  27. 27.
    Terry P, Bergkvist L, Holmberg L, Wolk A (2001) No association between fat and fatty acids intake and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 10:913–914PubMedGoogle Scholar
  28. 28.
    Limburg PJ, Liu-Mares W, Vierkant RA, Wang AH, Harnack L, Flood AP, Sellers TA, Cerhan JR (2008) Prospective evaluation of trans-fatty acid intake and colorectal cancer risk in the Iowa Women’s Health Study. Int J Cancer 123:2717–2719CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Astarci E, Bansan AEE, Banerjee S (2012) Matrix metalloprotease 16 expression is downregulated by microRNA-146a in spontaneously differentiating Caco-2 cells. Dev Growth Differ 54:216–226CrossRefPubMedGoogle Scholar
  30. 30.
    Schaefer JS, Montufar-Solis D, Vigneswaran N, Klein JR (2011) Selective upregulation of microRNA expression in peripheral blood leukocytes in IL-10(−/−) mice precedes expression in the colon. J Immunol 187:5834–5841CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Oberg AL, French AJ, Sarver AL, Subramanian S, Morlan BW, Riska SM, Borralho PM, Cunningham JM, Boardman LA, Wang L, Smyrk TC, Asmann Y, Steer CJ, Thibodeau SN (2011) miRNA expression in colon polyps provides evidence for a multihit model of colon cancer. PLoS One 6:e20465CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Sarver AL, French AJ, Borralho PM, Thayanithy V, Oberg AL, Silverstein KAT, Morlan BW, Riska SM, Boardman LA, Cunningham JM, Subramanian S, Wang L, Smyrk TC, Rodrigues CM, Thibodeau SN, Steer CJ (2009) Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer 9:401CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Wu W, Yang J, Feng X, Wang H, Ye S, Yang P, Tan W, Wei G, Zhou Y (2013) MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells. Mol Cancer 12:30CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Wu WY, Yang PC, Feng X, Wang H, Qiu YM, Tian T, He YT, Yu CY, Yang JF, Ye SC, Zhou Y (2013) The relationship between and clinical significance of MicroRNA-32 and phosphatase and tensin homologue expression in colorectal cancer. Genes Chromosomes Cancer 52:1133–1140CrossRefPubMedGoogle Scholar

Copyright information

© AOCS 2015

Authors and Affiliations

  • Solveigh Köpke
    • 1
  • Thorsten Buhrke
    • 1
    Email author
  • Alfonso Lampen
    • 1
  1. 1.Department of Food SafetyFederal Institute for Risk AssessmentBerlinGermany

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