Integrative p53, micro-RNA and Cathepsin Protease Co-Regulatory Expression Networks in Cancer

SIMPLE SUMMARY: This article describes an emerging area of significant interest in cancer and cell death and the relationships shared by these through the transcriptional regulation of cathepsin protease genes by micro-RNAs that are connected to p53 activation. While it has been demonstrated that the p53 protein can directly regulate some cathepsin genes and the expression of their upstream regulatory micro-RNAs, very little is known about what input the p53 isoform proteins may have in regulating this relationship. Herein, we draw attention to this important regulatory aspect in the context of describing mechanisms that are being established for the micro-RNA regulation of cathepsin protease genes and their collective use in diagnostic or prognostic assays. ABSTRACT: As the direct regulatory role of p53 and some of its isoform proteins are becoming established in modulating gene expression in cancer research, another aspect of this mode of gene regulation that has captured significant interest over the years is the mechanistic interplay between p53 and micro-RNA transcriptional regulation. The input of this into modulating gene expression for some of the cathepsin family members has been viewed as carrying noticeable importance based on their biological effects during normal cellular homeostasis and cancer progression. While this area is still in its infancy in relation to general cathepsin gene regulation, we review the current p53-regulated micro-RNAs that are generating significant interest through their regulation of cathepsin proteases, thereby strengthening the link between activated p53 forms and cathepsin gene regulation. Additionally, we extend our understanding of this developing relationship to how such micro-RNAs are being utilized as diagnostic or prognostic tools and highlight their future uses in conjunction with cathepsin gene expression as potential biomarkers within a clinical setting.