A Parallel Study of mRNA and microRNA Profiling of Peripheral Blood in Young Adult Women

Abstract

Background: Aging is a complex process that involves the interplay of genetic, epigenetic, and environmental factors. Identifying aging-related biomarkers holds great potential for improving our understanding of complex physiological changes, thereby providing a means to investigate the mechanism by which aging influences various diseases.

Method and results: We performed a parallel study of microRNA and gene expression profiling of peripheral blood in a group of healthy young adult women, among which 13 were aged 22-25 and 9 were aged 36-39 years old. We identified a significantly distinct pattern of microRNA, but not gene expression profiling, between these two young adult women groups. We also performed correlation analysis of expression levels between all pairs of age-associated microRNAs and genes and identified a weak global correlation between these two types of expression levels. A significant involvement of estrogen regulation was observed by pathway analysis of the most differentially expressed microRNAs that included miR-155, -18a, -142, -340, -363, -195, and -24.

Conclusion: Our results suggest that the change in global microRNA expression in the peripheral blood is associated with normal aging in young adult women. This change may precede global gene expression changes. Future studies are needed to investigate the regulatory mechanism of the estrogen-related microRNAs and associated diseases.

Keywords: aging; estrogen; gene expression; microRNA; microarrays.

Figure 1

Parallel comparison of miRNA and mRNA profiling patterns among 9 older (aged 36–39) and 13 younger (aged 22–25) adult women by principal component analysis. (A) miRNA profiling; (B) mRNA profiling. For the miRNA data, the first principal component (X-axis) explains 40.8% of total variation and the second principal component explains (Y-axis) 14.5% of total variation. For the mRNA data, the first and second principal components explain 18.4 and 13% of total variation, respectively. (C) Cluster analysis of miRNA profiling.

Figure 2

Distributions of p-values from t tests comparing younger and older women. (A) miRNA profiling; (B) mRNA profiling. The width of each bin represents an interval of 0.05 p-value. The horizontal dashed lines indicate the expected distribution under the null hypothesis of no differential expression. If there were no differential expression observed, all the bars will be approximately at the height of the dashed line.

Figure 3

Quantitative RT-PCR validation of four age-associated miRNAs identified from the microarray experiment. Bars represent fold changes comparing expression between older and younger women. A positive (negative) fold change represents up (down)-regulation of expression in older women.

Figure 4

An estrogen regulation network of age-associated differentially expressed miRNAs from Ingenuity Pathway Analysis. Dashed arrow: negative regulation; solid arrow: positive regulation. β-estradiol represents protein.