Tumor cell-derived exosome RNF126 affects the immune microenvironment and promotes nasopharyngeal carcinoma progression by regulating PTEN ubiquitination.

This study aimed to investigate the role and regulatory mechanism of RNF126 in nasopharyngeal carcinoma. Firstly, the expression and prognosis of RNF126 were analyzed by TCGA database. The expression of RNF126 was further verified by NPC tissue samples and cells. An ectopic xenograft model was constructed to verify the regulatory role of RNF126 in NPC tumor progression. The regulatory effect of RNF126 on macrophage polarization and migration was verified by co-culture of tumor cells and THP-1 cells. The role of RNF126 in tumor exosomes involved in intercellular communication was further verified by nanoparticle tracking technology, western blotting and immunofluorescence assays. QRT-PCR, half-life assay and WB assay were used to verify the regulatory effect of RNF126 on PTEN ubiquitination and PI3K/AKT pathway. Finally, an in vivo assay was used to verify the regulation of exosomes on tumor growth and metastasis. In summary, we found for the first time that tumor-derived exosomal PTEN degrades PTEN through ubiquitination to regulate the tumor immune microenvironment and promote NPC growth and metastasis. These results provide the basis for the screening of early markers of NPC and targeted therapy.