microRNA Dysregulation in Prostate Cancer: Network Analysis Reveals Preferential Regulation of Highly Connected Nodes

Abstract

microRNAs (miRNAs) are small RNAs shown to contribute to a number of cellular processes including cell growth, differentiation, and apoptosis. MiRNAs regulate gene expression of their targets post-transcriptionally by binding to messenger RNA (mRNA), causing translational inhibition or mRNA degradation. Dysregulation of miRNA expression can promote cancer formation and progression. Research has largely focused on the function and expression of single miRNAs. However, complex physiological processes require the interaction, regulation and coordination of many molecules including miRNAs and proteins. Highly connected molecules often serve important roles in the cell. A protein–protein interaction network of established miRNA targets confirmed these proteins to be highly connected and essential to the cell, affecting tumorigenesis, cell growth/proliferation, cellular death, cell assembly, and maintenance pathways. This analysis showed that miRNAs contribute to the overall health of the prostate, and their aberrant expression destabilized homeostatic balance. This integrative network approach can reveal important miRNAs and proteins in prostate cancer that will be useful to identify specific disease biomarkers, which may be used as targets for therapeutics or drugs in themselves.

Reconstruction and Analysis of Transcription Factor–miRNA Co-Regulatory Feed-Forward Loops in Human Cancers Using Filter-Wrapper Feature Selection

“…Finally, we compared the FFLs reconstructed from pan-cancer and prostate cancer datasets and identified 2 TF-FFLs (Figure 3B) that appeared in both datasets. Interestingly, the miRNAs in these two FFLs, hsa-let-7a and hsa-let-7e, belong to the hsa-let-7 family that is related to prostate [35], breast [36], lung [37] cancers.…”

Structure and dynamics of molecular networks: A novel paradigm of drug discovery

“…microRNAs involved in prostate cancer progression preferentially target interactome hubs (Budd et al, 2012). microRNA networks obtained from 3,312 neoplastic and 1,107 nonmalignant human samples showed the dysregulation of hub microRNAs.…”

The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis

“…Network analysis have shown that genes that are subject to extensive miRNAs regulation, referred as to target hubs, are more likely to be biologically relevant (30,31). In addition, it has been shown that many TFs are among these target hubs and there is increasing evidence of reciprocal regulation between miRNAs and TFs as well as the existence of extensive coordination in the regulation of shared targets genes at the genome-scale level (32,33).…”