[Frontiers in Bioscience 16, 3133-3145, June 1, 2011]

Structural evidence of anti-atherogenic microRNAs

Anthony Virtue1, Jietang Mai1, Ying Yin1, Shu Meng1, Tran Tran1, Xiaohua Jiang1, Hong Wang1, Xiao-Feng Yang1

1Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Introduction
3. Materials and methods
3.1. Compilation of an inflammatory gene list that is modulated in atherosclerotic lesions
3.2. Prediction of miRNAs which potentially target the list of pro-atherogenic inflammatory genes
3.3. Expression of miRNAs within vascular tissues and/or inflammatory cells
3.4. Statistical analysis
4. Results
4.1. Generation of a list of 33 inflammatory genes modulated in atherosclerotic lesions
4.2. Atherosclerotic inflammatory genes have structural features in the 3'UTR of their mRNAs receptive to potential miRNAs regulation
4.3. 21 out of 33 atherosclerotic inflammatory genes (64%) were targeted by highly expressed miRNAs
4.4. The miRNAs targeting atherosclerotic inflammatory genes use statistically higher numbers of "poorly conserved" bindings sites than a control group of miRNAs
5. Discussion
6. Acknowledgements
7. Disclosures
8. References

1. ABSTRACT

Our research attempted to address two important questions - how microRNAs modulate atherogenic inflammatory genes from a panoramic viewpoint and whether their augmented expression results from reduced microRNAs suppression. To resolve these knowledge gaps, we employed a novel database mining technique in conjunction with statistical analysis criteria established from experimentally verified microRNAs. We found that the expression of 33 inflammatory genes up-regulated in atherosclerotic lesions contain structural features in the 3'UTR of their mRNAs for potential microRNAs regulation. Additionally, the binding features governing the interactions between the microRNAs and the inflammatory gene mRNA were statistically identical to the features of experimentally verified microRNAs. Furthermore, 21 of the 33 inflammatory genes (64%) were targeted by highly expressed microRNAs and 10 of these (48%) were targeted by a single microRNA, suggesting microRNA regulation specificity. Supplementing our findings, 7 out of the 20 unique microRNAs (35%) were previously confirmed to be down-regulated when treated with pro-atherogenic factors. These results indicate a critical role of anti-inflammatory microRNAs in suppressing pro-atherogenic inflammatory gene expression.