YY1 enhances HIF-1α stability in tumor-associated macrophages to suppress anti-tumor immunity of prostate cancer

Prostate cancer, as an immune-cold tumor, shows poor response to immune checkpoint inhibitors, but the underlying mechanisms are not fully understood. Through YY1 proteomics experiments and RNA sequencing of THP-1 cells overexpressing YY1, combined with other biomolecular experiments, we demonstrated that hypoxia promotes the phosphorylation of YY1, thereby enhancing its binding to NUSAP1 and stabilizing HIF-1α, which in turn regulates the tumor microenvironment. Through bioinformatics techniques and in vitro protein IP experiments, we clarified that in tumor-associated macrophages, Tenapanor can competitively bind to the site to block the interaction between YY1 and NUSAP1, thereby affecting the stability of HIF-1α. To verify the therapeutic effects and mechanisms of Tenapanor on prostate cancer, we used the prostate cancer cell line RM1 to induce subcutaneous tumors in C57BL/6 mice. One week after tumor implantation, we administered TEN-M2pep or NC-M2pep (Tenapanor or control solvent ..., , # YY1 enhances HIF-1α stability in tumor-associated macrophages to suppress anti-tumor immunity of prostate cancer

Dataset DOI: [10.5061/dryad.rr4xgxdkn](10.5061/dryad.rr4xgxdkn)

## Description of the data and file structure

To elucidate the interactions of YY1 in macrophages, we conducted immunoprecipitation experiments in THP-1 cells followed by mass spectrometry analysis to identify proteins that interact with YY1.

Additionally, we performed bulk RNA sequencing on THP-1 cells overexpressing YY1 and those overexpressing a negative control (NC) to identify pathways regulated by YY1 in macrophages.

To investigate the therapeutic effects and mechanisms of Tenapanor on prostate cancer, and to specifically target tumor-associated macrophages (TAMs) in the tumor microenvironment, we utilized a liposome carrier conjugated with the TAM-targeting peptide M2pep (sequence: YEQDPWGVKWWY) to deliver Tenapanor (TEN-M2pep) or a control solvent (NC-M2pep). This delivery system was applied in a s...,