Fig. 6
From: Causative role of PDLIM2 epigenetic repression in lung cancer and therapeutic resistance
PDLIM2 represses STAT3 and RelA to increase MHC-I and repress cancer-related genes for suppressing lung cancer development and therapeutic resistance. a IHC staining showing increased nuclear RelA and STAT3 in lung cancers by PDLIM2 deletion in urethane model (n = 5). Scale bar, 10 μm. b Nuclear fraction-IB assays showing increased proteasomal degradation and decreased expression of nuclear RelA and STAT3 in the indicated human lung cancer cells reconstituted with PDLIM2 in the presence or absence of the proteasome inhibitor MG132. c K-RasG12D model showing suppression of increased lung tumors in PDLIM2−/− mice by tumor-selective RelA or STAT3 deletion. Mouse numbers: WT, 10; PDLIM2−/−, 7; PDLIM2−/−STAT3ΔLung, 6; PDLIM2−/−RelAΔLung, 5; STAT3ΔLung, 12; RelAΔLung, 2. d Cell growth assays showing decreased growth of the indicated human lung cancer cells by RelA or STAT3 shRNA knockdown (KD) (n = 3). e qPCR analysis showing decreased expression of the indicated growth-related genes in the indicated human lung cancer cells by RelA or STAT3 KD (n = 3). f qPCR analysis showing increased H2-K1 expression in lung tumors by STAT3 deletion (n ≥ 7) but not RelA deletion (n ≥ 2) (urethane model). g Subcellular fraction-IB assays showing much lower paclitaxel induction of nuclear RelA in H460 human lung cancer cells reconstituted with PDLIM2. h Cell growth assays showing increased paclitaxel sensitivity of H460 cells by stable IκBα expression (n = 3). Student’s t test (two tailed, unpaired) was performed in (a, c–f, h). Data represent means ± SEM in (a, c–f). *P < 0.05; **P < 0.01; ns, not statistically significant.
