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Review
, 18, 927-937

Exploring the Potential of MicroRNA Let-7c as a Therapeutic for Prostate Cancer

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Review

Exploring the Potential of MicroRNA Let-7c as a Therapeutic for Prostate Cancer

Eoghan J Mulholland et al. Mol Ther Nucleic Acids.

Abstract

Prostate cancer (PCa) is one of the leading causes of mortality worldwide and often presents with aberrant microRNA (miRNA) expression. Identifying and understanding the unique expression profiles could aid in the detection and treatment of this disease. This review aims to identify miRNAs as potential therapeutic targets for PCa. Three bio-informatic searches were conducted to identify miRNAs that are reportedly implicated in the pathogenesis of PCa. Only hsa-Lethal-7 (let-7c), recognized for its role in PCa pathogenesis, was common to all three databases. Three further database searches were conducted to identify known targets of hsa-let-7c. Four targets were identified, HMGA2, c-Myc (MYC), TRAIL, and CASP3. An extensive review of the literature was undertaken to assess the role of hsa-let-7c in the progression of other malignancies and to evaluate its potential as a therapeutic target for PCa. The heterogeneous nature of cancer makes it logical to develop mechanisms by which the treatment of malignancies is tailored to an individual, harnessing specific knowledge of the underlying biology of the disease. Resetting cellular miRNA levels is an exciting prospect that will allow this ambition to be realized.

Keywords: CASP3; Let-7; gene therapy; microRNA; prostate cancer.

Figures

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Figure 1
Figure 1
miRNA Biogenesis The miRNA is translated by RNA polymerase II to form a pri-miRNA. The RNase III enzyme DROSHA cuts the single-stranded RNA/double-stranded RNA (ssRNA/dsRNA) junction to create a pre-miRNA. The pre-miRNA is transported to the cytoplasm via EXPORTIN 5/RAN-GTP. It then undergoes modification by DICER. The guide strand is then incorporated into the RNA-induced silencing complex (RISC), where it leads the complex toward target mRNA transcripts.
Figure 2
Figure 2
A Venn Diagram Displaying Database Analysis Results Using miRCancer, miR2Disease, and PhenomiR2 Databases One target, hsa-let-7c, was common to all three databases.
Figure 3
Figure 3
Schematic Diagram of the Lin28B/MYC/Let-7 Interaction Let-7 maturity blocks the transcription of Lin28B and MYC. In the presence of Lin28B, pri-let-7 and pre-let-7 processing is inhibited. Repression of mature let-7 triggers an upsurge in MYC and Lin28B expression.
Figure 4
Figure 4
A Venn Diagram Displaying let-7c Database Targets Using miRSearch 3, miRSel, and starBase 2 Databases In total, four hsa-let-7c targets were identified as being common to all three databases.
Figure 5
Figure 5
A Schematic Diagram Showing Targets of let-7 in Cancer Let-7 causes translational suppression of HMGA2, MYC, TRAIL, CASP3, and Lin28B. Blockage of let-7 biogenesis will consequently result in an upregulation of each of these targets. Lin28B and TRAIL-receptor 2 further contribute to the inhibition of let-7 biogenesis. Collectively, upregulation of these targets results in a proliferative, invasive, and therapeutically resistant phenotype.

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