MicroRNA expression and function in prostate cancer: a review of current knowledge and opportunities for discovery

Binod Kumar, Shawn E Lupold, Binod Kumar, Shawn E Lupold

Abstract

MicroRNAs (miRNAs) are well-conserved noncoding RNAs that broadly regulate gene expression through posttranscriptional silencing of coding genes. Dysregulated miRNA expression in prostate and other cancers implicates their role in cancer biology. Moreover, functional studies provide support for the contribution of miRNAs to several key pathways in cancer initiation and progression. Comparative analyses of miRNA gene expression between malignant and nonmalignant prostate tissues, healthy controls and prostate cancer (PCa) patients, as well as less aggressive versus more aggressive disease indicate that miRNAs may be future diagnostic or prognostic biomarkers in tumor tissue, blood, or urine. Further, miRNAs may be future therapeutics or therapeutic targets. In this review, we examine the miRNAs most commonly observed to be de-regulated in PCa gene expression analyses and review the potential contribution of these miRNAs to important pathways in PCa initiation and progression.

Figures

Figure 1
Figure 1
Opportunities and unmet needs in the progression of prostate cancer. The natural progression of prostate cancer from initiation to castration-resistant metastatic disease is highlighted. The upper right quadrant indicates the most common methods for management and therapy as the disease progresses. The lower left quadrant indicates resources for miRNA discovery and biomarker analyses and the potential areas for utility, such as diagnosis or active surveillance.
Figure 2
Figure 2
miRNA biogenesis. Schematic representation of miRNA biogenesis initiating with primary miRNA (pri-miRNA) transcription. Boxes indicate miRNA biogenesis components that have been reported to be deregulated in human PCa. References (ref) are indicated.
Figure 3
Figure 3
miRNAs in the molecular progression of prostate cancer. Schematic representation of key pathways in the molecular and genetic progression of PCa. miRNAs previously identified to directly regulate each molecule in cellular models of prostate cancer are provided. Those in green font indicate miRNAs that are implicated in regulation, but which have not yet been directly demonstrated in prostate models.

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