Objective  To explore the combined killing effect of inhibiting the expression of protein arginine methyltransferase 5 (PRMT5) gene on methylthioadenosine phosphorylase (MTAP) deficient malignant pleural mesothelioma (MPM) cells.

  Methods  MPM cells were divided into MTAP positive group (REN, H28 and MPP89) and MTAP deficient group (H2591, 2452 and H2052), and the Hap-1 MTAP KO/WT were used as controls. PRMT5 siRNA and quinacrine (0, 0.5 and 1.0 μmol/L) were used to treat cells in two groups, and the expression levels of PRMT5 protein and H4R3me2s methylated protein were detected by Western blot after 72 hours. The ability of cell clone and proliferation was determined by crystal violet staining.

  Results  PRMT5 siRNA was able to downregulate the PRMT5 protein levels of MTAP positive cell lines and MTAP deficient cell lines, resulting in a significant decrease in the H4R3me2s methylation level of MTAP deficient MPM cells, but had no significant inhibitory effects on the H4R3me2s methylation level of MTAP positive cells. PRMT5 siRNA was able to inhibit the clonal and proliferation ability of MTAP deficient cells, but had no significant inhibitory effect on the cloning of MTAP positive cells (P=0.023, n=3). Quinacrine was able to downregulate the expression level of PRMT5 protein in MTAP deficient cell lines (H2591 and H2052), reduce the methylation level of H4R3me2s and the ability of cell clone and proliferation, but had no down-regulation effect on PRMT5 and H4R3me2s in MTAP positive cell lines (MPP89)and no inhibitory effect on cell proliferation, and there were significant differences (P=0.018, n=3).

  Conclusion  Inhibition of PMRT5 can kill MTAP deficient MPM in combination, and quinacrine can produce combined killing effect on some MTAP deficient MPM.