MicroRNA-5581-5p: A Novel tumor suppressor in Mesothelioma

Authors

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

Abstract

Diffuse pleural mesothelioma (DPM) is an aggressive cancer, difficult to cure with unique pathobiology and low survival rate. Prolonged latency makes DPM difficult to prognose, diagnose and treat patients. microRNA (miRNA) dysregulation has already been shown in cancer leading to tumor cells evasion from apoptosis and increased proliferation. Recent studies showed that miRNA dysregulation plays important role in mesothelioma pathogenesis, and function as tumor suppressor. Study aims to identify novel mesothelioma specific anti-tumorigenic miRNAs using human miRNA libraries.
Two human microRNA-mimic libraries, Ambion and Dharmacon, was used to identify novel potent anti-tumor miRNAs in mesothelioma using high-throughput screening (HTS). miRNAs expressions were analyzed by q-PCR in DPM cells compared to normal mesothelial cells. For functional assays, proliferation, 2D foci formation, 3D spheres formation, and apoptosis activity, multiple DPM cell were transfected with miRNA-5581-5p or negative control mimic. Protein levels were quantitated by Western blot.
HTS identified top10 microRNAs which consistently exhibited antitumor activity across a panel of DPM cells. One of top 10 miRNA candidate, miR-5581-5p was drastically downregulated in DPM cells as compared to normal pleural cells. Re-introduction of mir5581-5p reduces the growth of DPM cells as evident from the 2D colony foci and 3D sphere formation. mir5581-5p treatment induces apoptosis. Furthermore, apoptosis was confirmed by increase cleaved caspase-3 and PARP activity in mir5581-5p treated DPM cells.
Our study concludes, mir5581-5p as a novel tumor suppressor miRNA which inhibits the growth of DPM functioning as tumor suppressor. These data suggest that miR-5581-5p has a promising therapeutic potential for DPM.

Scientific Focus Area: RNA Biology

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