Pathobiology 2023 Febrary 1 [Link]

Ihiro Endo, Vishwa Jeet Amatya, Kei Kushitani Tetsuya Nakagiri, Kohei Aoe, Yukio Takeshima


Introduction: Malignant mesothelioma is an aggressive cancer associated with asbestos exposure. Currently, the efficacy of therapeutics is limited in malignant mesothelioma, and developing more effective therapies is the need of the hour. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), have attracted attention as therapeutic targets. To explore potential therapeutic targets, we focused on miR-142-3p expression, which was found to be significantly downregulated in mesothelioma cell lines in our previous study.

Methods: Mesothelioma cell lines and tissues were validated for expression of miR-142-3p or integrin subunit alpha-V (ITGAV). We transfected mesothelioma cell lines with miR-142-3p mimic and ITGAV siRNA and analyzed their biological functions.

Results: We found that miR-142-3p was significantly downregulated in mesothelioma tissues. Transfection with miR-142-3p mimic significantly suppressed cell proliferation, migration, and invasion. Bioinformatics analysis of potential targets of miR-142-3p identified ITGAV. Membrane ITGAV expression in mesothelioma cell lines was confirmed using immunocytochemistry. ITGAV was significantly upregulated in mesothelioma tissues. Moreover, transfection of miR-142-3p mimics into mesothelioma cell lines significantly suppressed ITGAV expression, indicating that miR-142-3p targets ITGAV. Next, ITGAV siRNA transfection into mesothelioma cell lines inhibited cell proliferation, migration, and invasion. Further investigation of cell adhesion mechanisms showed that the miR-142-3p/ITGAV axis specifically affects mesothelioma cell adhesion via vitronectin in the extracellular matrix.

Conclusion: This study proposed that the miR-142-3p/ITGAV axis is involved in tumor progression in malignant mesothelioma.