Fig. 6: A small molecule inhibitor targeting the YY1–NUSAP1–HIF-1α interaction suppressed PCa progression.

a Schematic diagram showing that tenapanor inhibits the binding of the YY1–NUSAP1–HIF-1α nexus. b, c Co-IP of NUSAP1 showed that its interactions with YY1 and HIF-1α were suppressed by tenapanor. The protein intensity of YY1 and HIF-1α pulled down from NUSAP1 was analyzed with ImageJ and standardized to that of the input samples from the same experiment. The blots were processed in parallel (n = 3 independent experiments, P < 0.001 and P < 0.001). *P < 0.05. d, e Schematic diagram and tumor growth curve of the effects of TEN-M2pep and control medium on subcutaneous tumorigenesis in mice. Each experimental group consisted of five male C57BL/6 mice, all aged 6–8 weeks. The right panels present the mean values ± SD at each time point (n = 5 independent experiments, one-way ANOVA followed by Tukey test based on data in the last time point). f, g GO analysis based on RNA-sequencing data of CD45-sorted cells from TEN-M2pep-treated subcutaneous tumors showing enriched immune response-related pathways and representative upregulated genes (two-tailed t-test). h, i Immunohistochemical staining and flow cytometry of subcutaneous tumors showing the infiltration of CD8⁺ T cells in the indicated groups (n = 3 independent experiments, P = 0.019 and P = 0.002). Bar graphs (c, i) present the mean values ± SD, and the p values are calculated using a two-tailed t-test. * P < 0.05. Source data are provided as a Source Data file.