miR-1293 as a Potential Therapeutic Agent in Diffuse Pleural Mesothelioma: Targeting DNA Repair Pathways

Authors

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

Abstract

Diffuse pleural mesothelioma (DPM) is a highly aggressive cancer with limited treatment options. MicroRNA (miRNA) dysregulation plays a critical role in cancer progression, and recent studies suggest miRNAs can act as tumor suppressors in mesothelioma.
This study aimed to identify novel anti-tumorigenic miRNAs for mesothelioma using a human miRNA library. Screening identified miR-1293 as a top candidate due to its significant antiproliferative effects on mesothelioma cell lines. The expression of miR-1293 was validated using quantitative real-time PCR in DPM patients (Normal=21, Tumor=56) and cell lines. Ectopic expression of miR-1293 was achieved by mimic transfection in DPM cells, followed by various phenotypic and functional assays, including proliferation and apoptosis measurements.
Re-expression of miR-1293 in DPM cells resulted in significant cell death and reductions in colony formation, 3D spheroid growth, and soft agar growth. miR-1293-treated cells showed increased apoptosis, confirmed by elevated caspase 3/7 activity and higher levels of cleaved PARP, and induced G2/M phase cell cycle arrest. TargetScan predicted BRD4, APEX1, RPA1, and POLD4 as direct targets of miR-1293. Downregulation of these DNA repair genes by miR-1293 treatment impaired DNA repair mechanisms, thereby suppressing DPM cell growth.
miR-1293 re-expression exerts tumor-suppressive effects in DPM by downregulating key DNA repair pathway genes. These findings support further development of miR-1293 as a promising therapeutic agent for DPM in preclinical models.

Scientific Focus Area: Cancer Biology

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