miR-342-5p as a Tumor Suppressor: A Promising Therapeutic Candidate for Diffuse Pleural Mesothelioma

Authors

• SH Yoon
• A Singh
• N Pruett
• V Singh
• S Sahu
• CD Hoang

Abstract

Diffuse pleural mesothelioma (MPM) is an incurable and aggressive neoplasm arising from mesothelial cells, with limited therapeutic options available. In various cancers, multiple microRNAs (miRNAs) are lost due to their location in genomic fragile sites. Utilizing tumor-suppressive miRNAs presents an attractive alternative therapeutic approach, and we posit that the biological effects of miRNAs can disrupt the molecular networks associated with DPM pathogenesis.

In our study, we screened for potential miRNAs with antiproliferative effects on mesothelioma cell lines using a human miRNA mimic library. Among the candidates, miR-342-5p emerged as one of the top miRNAs exhibiting significant anti-tumor activity across a panel of DPM cell lines. We further validated the downregulation of miR-342-5p expression in DPM patients (Normal=22, Tumor=50) and DPM cells using quantitative real-time PCR. TCGA data analysis also revealed that miR-342-5p downregulation is associated with poor survival outcomes.

Functional assays demonstrated that the re-expression of miR-342-5p significantly impaired MPM cell viability, reduced 2D colony foci formation, and inhibited anchorage-independent cell growth in soft-agar and sphere assays. Additionally, Annexin-V assays showed a significant increase in early and late apoptotic cells in miR-342-5p transfected DPM cells compared to controls. Importantly, when normal mesothelial cells (NP1) were treated with miR-342-5p, no significant biological effects were observed.

Altogether, our findings suggest that miR-342-5p functions as a tumor suppressor and represents a potential therapeutic miRNA candidate for the treatment of mesothelioma. This study underscores the promise of miRNA-based therapies in combating this formidable malignancy, providing a new avenue for clinical intervention.

Scientific Focus Area: RNA Biology

This page was last updated on Tuesday, August 6, 2024