Fig. 4

STAT3-mediated G9a facilitated the expression of ERBB3. a Knockdown of STAT3 in A549 cells reduced cell viability in vitro, and b and c in vivo in a tumor xenograft model. Tumors are indicated by arrows. d There were 245 common genes between RNAseq data from A549shSTAT3 (Additional file 4: Table S4) and A549shG9a (Additional file 5: Table S5), e including ERBB3 after NetworkAnalyst analysis. In addition, ERBB2 expression decreased only in A549shSTAT3. The data revealed that G9a led to ERBB3 expression in A549 cells. f To validate the assumption, ERBB3 was detected by qPCR in EGF-treated A549shG9a cells compared with A549shLuc cells. The results indicated that ERBB3 decreased in A549shG9a cells with or without EGF treatment. g The results from Western blot analyses revealed that EGF induced STAT3 phosphorylation resulting in G9a and ERBB3 overexpression. Knockdown of G9a reduced the EGF-mediated ERBB3 expression without influencing STAT3 phosphorylation in A549 cells, demonstrating that G9a facilitated ERBB3 expression. h In addition, G9a inhibitors, UNC0642 and BIX01294, significantly blocked G9a-mediated di-mH3K9 activity and reduced ERBB3 expression in EGFR-autophosphorylated lung cancer H1975 cells. i Meanwhile, overexpression of G9a increased ERBB3 expression in A549 cells. *p < 0.05, ***p < 0.001