Fig. 6

HIF-1α is a critical effector of PTBP3-mediated malignant features in colon cancer. a HCT116 cells ± PTBP3 KD were co-transfected with expression vectors encoding either empty vector, mutant HIF-1α and assessed by Western blot for HIF1α and PTBP3 expression. GAPDH was used as a loading control. b Effects of ectopic expression of mutant HIF-1α on migration capacity of HCT116 cells with PTBP3 KD. c Effects of ectopic expression of mutant HIF-1α on invasive capacity of HCT116 cells with PTBP3 KD. d HCT116 and SW480 cells cells ± PTBP3 OE was treated with HIF-1α inhibitor 2-Methoxyestradiol (2-MeOE2, 10 μM.) and assessed by Western blot for HIF1α and PTBP3 expression. GAPDH was used as a loading control. e Effects of 2-MeOE2 on migration capacity of HCT116 cells ± PTBP3 OE. f Effects of 2-MeOE2 on invasive capacity of HCT116 cells ± PTBP3 OE. g Effects of 2-MeOE2 on migration capacity of SW480 cells ± PTBP3 OE. h Effects of 2-MeOE2 on invasive capacity of SW480 cells ± PTBP3 OE. i-k Effect of 2-MeOE2 on the subcapsular tumor xenografts growth formed by injection of HCT116 cell ± PTBP3 OE, as assessed by evaluating tumor weight (j) and tumor volume (k). 2-MeOE2 was used at a dose of 50 mg/kg per day by means of intragastric administration for one week. l Correlation analysis of relative mRNA levels of PTBP3 and VEGFA, HK2, PLOD2 or LDHA using the GEO dataset (GSE40976), contains 566 CRC tissues. m A cartoon summarizing our findings. PTBP3 promotes HIF-1α protein expression through binding to the IRES sequences of the HIF-1α mRNA 5’UTR to enhance HIF-1α translation in CRC, thereby promoting colon cancer growth, and metastasis. Data are presented as the means ± SD for experiments in triplicate. ***p < 0.001