Date of this Version
Howard, K. (2015) Stability and Biological Activity of Dietary MicroRNAs. MS thesis, University of Nebraska-Lincoln.
MicroRNAs play important roles in gene regulation by binding to complimentary sites at the 3’ untranslated region of target mRNA molecules. Binding results in inhibition or degradation of target mRNA. Many bovine and chicken microRNA are homologous with human counterparts enabling gene regulation. A recent study in our lab provided undisputable evidence that endogenous milk microRNAs are bioavailable in humans; resulting in regulation of human gene expression. Based on these findings, we wanted to explore the possibility that other exogenous food borne microRNAs are able to be absorbed through the diet. My thesis surrounds two aims: 1) assessing the stability of milk borne microRNAs and 2) analyzing the bioavailability of egg borne microRNAs and effects on gene expression following an egg meal.
Aim 1: We assessed the effects of milk processing, storage, somatic cell content and handling by consumers on the degradation of miRNAs in milk. Pasteurization and homogenization caused a 63% loss of miR-200c, whereas a 67% loss observed for miR-29b was statistically significant only in skim milk. Effects of cold storage and somatic cell content were quantitatively minor.
Aim 2: Humans absorbed a significant amount of egg borne microRNAs following an egg meal. Increased plasma levels of miR-181b from baseline showed to be dose dependent. Plasma concentrations of miR-181b peaked 9 hours after egg consumption to 150% above baseline levels. The abundance of miR-181a was also increased in erythrocytes 9 hours after egg consumption to levels 154% higher than baseline values. Expression of BCL2 and BCL2A1, experimentally validated targets of miR-181a/b, was 56% and 19% lower, respectively, in human lymphocytes nine hours after egg consumption.
Advisor: Janos Zempleni