Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma

Abstract

Malignant mesothelioma is an aggressive and often fatal cancer associated with asbestos exposure. The disease originates in the mesothelial lining of the serosal cavities, most commonly affecting the pleura. Survival rates are low as diagnosis often occurs at an advanced stage and current treatments are limited. Identifying new diagnostic and therapeutic targets for mesothelioma remains a priority, particularly for the new wave of victims exposed to asbestos through do-it-yourself renovations and in countries where asbestos is still mined and used. Recent advances have demonstrated a biological role for the small but powerful gene regulators microRNA (miRNA) in mesothelioma. A number of potential therapeutic targets have been identified. MiRNA have also become popular as potential biomarkers for mesothelioma due to their stable expression in bodily fluid and tissues. In this review, we highlight the current challenges associated with the diagnosis and treatment of mesothelioma and discuss how targeting miRNA may improve diagnostic, prognostic and therapeutic approaches.

Keywords: biomarkers; malignant peritoneal mesothelioma; malignant pleural mesothelioma; microRNA; therapies.

Figure 1. miRNA biogenesis

MiRNA biogenesis starts in the nucleus where the miRNA gene is transcribed into a primary miRNA transcript (pri-miRNA) and processed by Drosha/DGCR8 into the miRNA precursor (pre-miRNA). The precursor is exported into the cytoplasm by Exportin-5 where it is cleaved by Dicer to become the mature miRNA. This strand forms the miRISC complex with the AGO2, TRBP, PACT and Dicer proteins. The miRISC uses the miRNA as a guide to identify and bind to target mRNA causing the inhibition of target genes by inducing mRNA degradation or inhibiting translation.