ProatherogenIc Inflamatory mRNAs Have structural Features for Being Regulated by MicroRNAs

Abstract 5316

The current literature focusing on miRNAs has failed to adequately address two important questions - how miRNAs modulate atherogenic inflammatory genes from a panoramic viewpoint and whether the augmented expression of the atherogenic inflammatory genes is the result of miRNAs suppression. To resolve these knowledge gaps, we have employed a novel database mining technique in conjunction with statistical analysis criteria established from experimentally verified miRNAs. Utilizing this strategy we were able to conclude that the expression of 33 inflammatory genes is upregulated in atherosclerotic lesions and that these genes contain structural features in the 3'UTR of their mRNA for potential miRNAs regulation. Additionally, the binding features governing the interactions between the miRNAs and the inflammatory genes were statistically identical to the features of experimentally verified miRNAs. It was also determined that 21 (64%) of the 33 inflammatory genes were targeted by highly expressed miRNAs while the remaining 12 genes (36%) were targeted by normally expressed miRNAs. In addition, 10 of the 21 highly expressed miRNA-targeted inflammatory genes (48%) were targeted by a single miRNA, suggesting miRNA regulation specificity. Furthermore, 12 (48%) out of the 25 miRNAs found to meet our criteria targeted individual inflammatory genes while the other 13 miRNAs targeted multiple inflammatory genes. These results indicate a critical role of miRNAs in regulating proatherogenic inflammatory gene expression.