Fig. 4: IOX1 downregulates P-gp and PD-L1 expression through JMJD1A/β-catenin signaling pathway.
From: Co-delivery of IOX1 and doxorubicin for antibody-independent cancer chemo-immunotherapy
a The pathway by which JMJD1A promotes P-gp and PD-L1 expression in tumour cells. The overexpressed JMJD1A increases the nuclear enrichment of β-catenin, which in turn accelerates the transcription and translation of downstream targets, including P-gp and PD-L1. b–e Effects of JMJD1A-knockdown on protein expressions measured by western blotting (b,c) or gene expressions measured by qPCR (d,e) in CT26 (b,d) or HCT116 (c,e) cells; 4 × 105 cells were transfected with shJmjd1a (2 μg/well) for 48 h; n = 3 independent experiments in (d,e). f,g Effects of β-catenin rescue in JMJD1A-knockdown CT26 cells on the P-gp and PD-L1 expressions: (f) the relative protein levels and (g) mRNA levels of JMJD1A (Jmjd1a), β-catenin (Ctnnb1), P-gp (Abcb1) and PD-L1 (Cd274) in CT26 cells; 4 × 105 cells were transfected with shJmjd1a (2 μg/well) for 48 h followed by transfection with Ctnnb1 plasmid (2 μg/well) for 24 h; n = 3 independent experiments in (g). h,i IOX1 dose-dependent reduction of JMJD1A and β-catenin protein levels in CT26 (h) and HCT116 (i) cells; 24 h treatment. In (b,c,f,h,i), the experiments were repeated independently three times to confirm the results. Data represent mean ± SD. Two-tailed Student’s t test. ***P < 0.001, ****P < 0.0001. Source data are provided as a Source Data file.
