Fig. 5

G9a induced ERBB3 expression via the repression of miR-145-5p. a Western blot analysis revealed that the knockdown of ILF3 and G9a led to a reduction in HER3 (ERBB3) expression in A549 cells. There was a reduction of G9a in A549ILF3 cells, whereas demethylation of H3K9 presented G9a activity. b The gene cluster profiles in A549shILF3 and A549shG9a were listed and compared following small RNAseq analysis, c which revealed that 124 and 75 miRNAs were upregulated and downregulated, respectively, in A549shILF3 (Additional file 7: Table S7), and 62 and 48 miRNAs were upregulated and downregulated, respectively, in A549shG9a cells compared with A549shLuc cells (Additional file 8: Table S8). d There were 24 miRNAs with increased expression that were common between A549ILF3 and A549shG9a, and 3 potential miRNAs involved in HER3 expression, which were compared with the HER3-targeted miRNAs from TargetScan, including miR-130a-3p, miR-145-5p, and miR-19-3p. In addition, miRNA-145-5p transfection into A549 cells reduced HER3 expression detected by qPCR. e The expression of miRNA-145-5p in HCC827 cells was higher than in A549 and H1975 cells. f BBI608 (1 μg/mL) treatment significantly increased miR-145-5p expression in A549 cells. g In addition, the miRNA-145-5p level significantly increased in A549shG9a compared with in A549shLuc cells, which reduced in EGF treatment. h Therefore, co-treatment of afatinib with UNC0642 significantly reduced HCC827-derived tumorsphere formation based on tumorsphere diameter. i and j Therefore, targeting G9a by UNC0642 also reduced cell migration in A549 cells in a dose-dependent manner. *p < 0.05, **p < 0.01, ***p < 0.001. Scale bar, 100 μm