International Journal of Molecular Medicine 2021 June [Link]

Silvana Pinelli, Rossella Alinovi, Diana Poli, Massimo Corradi, Giorgio Pelosi, Marcello Tiseo, Matteo Goldoni, Delia Cavallo, Paola Mozzoni

Abstract

Dysregulated levels of microRNAs (miRNAs or miRs), involved in oncogenic pathways, have been proposed to contribute to the aggressiveness of malignant pleural mesothelioma (MPM). Previous studies have highlighted the downregulation of miRNA miR‑486‑5p in patients with mesothelioma and the introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important therapeutic strategy. The aim of the present study was to evaluate the mechanisms through which miRNAs may influence the functions, proliferation and sensitivity to cisplatin of MPM cells. In the present study, a miR‑486‑5p mimic was transfected into the H2052 and H28 MPM cell lines, and cell viability, proliferation, apoptosis and mitochondrial membrane potential were monitored. miR‑486‑5p overexpression led to a clear impairment of cell proliferation, targeting CDK4 and attenuating cell cycle progression. In addition, transfection with miR‑486‑5p mimic negatively regulated the release of inflammatory factors and the expression of Provirus integration site for Moloney murine leukaemia virus 1 (PIM1). The sensitivity of the cells to cisplatin was enhanced by enhancing the apoptotic effects of the drug and impairing mitochondrial function. On the whole, the present study demonstrates that miR‑486‑5p may play an important role in MPM treatment by targeting multiple pathways involved in tumour development and progression. These activities may be mostly related to the downregulation of PIM1, a crucial regulator of cell survival and proliferation. Furthermore, these results provide support for the combined use of miR‑486‑5p with chemotherapy as a therapeutic strategy for MPM.