Fig. 7: IRF4 is a tumor suppressor in BC re-expressed upon co-treatment with C29 and 5-azadC.
From: Inhibition of DNMT1 and ERRα crosstalk suppresses breast cancer via derepression of IRF4
a Agarose gel electrophoresis showing PCR product amplification of IRF4 cDNA following treatment with C29 (5 μM), 5-azadC (3 μM) or a combination of both drugs for 7 days in SKBR3 cells. b Relative mRNA levels of IRF4 in SKBR3 cells infected with shRNAs against IFR4 after treatment with C29 (5 μM), 5-azadC (3 μM) or a combination of both drugs for 7 days. c Normalized cell index curves representing proliferation of SKBR3 cells infected with either a control shRNA (shNTC) or two different shRNAs against IRF4 in the presence of C29 (5 μM) and 5-azadC (3 μM). Data represent one experiment performed with five replicates. d, e Kaplan–Meier survival curves representing the positive correlation between IRF4 mRNA expression and overall survival of BC patients in two independent cohorts consisting of 158 patients (GSE3143) (d) and 155 patients (GSE7390) (e). f Model illustrating how pharmacological inhibition of the inter-connected factors ERRα and DNMT1 can halt BC progression by simultaneously repressing methionine cycle metabolism and DNA methylation. Consequent epigenetic modulation impinges on the newly attributed tumor suppressor gene IRF4 in BC with C29 and 5-azadC co-treatment promoting IRF4 derepression. Data shown in b and c represent means ± SEM. *p < 0.05, ***p < 0.001; Student’s t test.
