Differential expression of microRNAs in different disease states

Abstract

Disturbances in gene expression as a result of perturbed transcription or posttranscriptional regulation is one of the main causes of cellular dysfunction that underlies different disease states. Approximately a decade ago, the discovery of microRNAs in mammalian cells has renewed our focus on posttranscriptional regulatory mechanisms during pathogenesis. These tiny posttranscriptional regulators are differentially expressed in almost every disease that has been studied to date and can modulate expression of a gene via specifically binding to its messenger RNA. Because of their capacity to simultaneously target multiple functionally related, genes, they are proving to be potentially powerful therapeutic agents/targets. In this review, we focus on the microRNAs that are differentially regulated in the more common cardiovascular pathologies, their targets, and potential function.

Figure 1. A diagram showing miRNAs and their targets in cardiac hypertrophy

The diagram displays the different miRNAs and their targets that are involved in gene switching, cellular hypertrophy, fibrosis, and electrical remodeling during cardiac hypertrophy. Upregulation or downregulation of a specific miRNA is represented by an upward (black) or a downward (red) arrow, respectively. The change in the expression levels of target genes inversely correlates with that of the targeting miRNA and is similarly represented by an up or down arrow. All listed targets have been validated. The listed targets include: thyroid hormone receptor-associated protein 1 (Thrap1), SRY-box containing gene 6 (Sox6), thyroid hormone receptor beta (Thrb), calmodulin, myocyte enhancer factor 2A (Mef2a), insulin-like growth factor 1 (IGF1), myostatin, muscle-specific RING finger protein 1 (MuRF1), dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (Dyrk1a), sprouty 2/4 (SPRY2/4), connective tissue growth factor (CTGF), collagen IA1 (Col1A1), GATA binding protein 4 (GATA4), phospholipase C beta 1 (PLCβ1), protein phosphatase 2, regulatory subunit B (B56) alpha isoform (Ppp2r5a), protein phosphatase 2 catalytic subunit (PP2Ac) and, the indirect targets alpha and beta myosin heavy chain (αand βMyh),

Figure 2. A diagram showing miRNAs and their targets in cardiac ischemia

The diagram displays the different miRNAs and their targets that are involved in cell viability, angiogenesis, fibrosis, and electrical remodeling during cardiac ischemia. Upregulation or downregulation of a specific miRNA is represented by an upward (black) or a downward (red) arrow, respectively. The change in the expression levels of target genes inversely correlates with that of the targeting miRNA and is similarly represented by an up or down arrow. All listed targets have been validated. The listed targets include: hypoxia-inducible factor 1 alpha (Hif-1α), sirtuin 1 (Sirt1), heat shock protein 20, 60, and 70 (HSP20, HSP60, HSP70), programmed cell death 4 (PDCD4), phosphatase and tensin homolog (PTEN), fas ligand (FasL), caspase 9, Rho-associated coiled-coil containing protein kinase 1 (Rock1), calmodulin kinase II delta (CAMKIIδ), BCL2-like 11 (Bim), ADP-ribosylation factor-like 2 (Arl2), B-cell CLL/lymphoma 2 (Bcl2), ephrin A3 (Ephna3), integrin, alpha 5 (ITGA5), sprouty-related, EVH1 domain containing 1 (SPRED1), GATA binding protein 2 (GATA2), p21 protein (Cdc42/Rac)-activated kinase 4 (PAK4), cullin 2 (cul2), connexin 43 (Cx43), inward rectifier potassium channel 2 (Kir2.1).