Tumor exosome promotes Th17 cell differentiation by transmitting the lncRNA CRNDE-h in colorectal cancer

The T helper 17 (Th17) cells in tumor microenvironment play an important role in colorectal cancer (CRC) progression. This study investigated the mechanism of Th17 cell differentiation in CRC with a focus on the role of tumor exosome-transmitted long noncoding RNA (lncRNA). Exosomes were isolated from the CRC cells and serum of CRC patients. The role and mechanism of the lncRNA CRNDE-h transmitted by CRC exosomes in Th17 cell differentiation were assessed by using various molecular biological methods. The serum exosomal CRNDE-h level was positively correlated with the proportion of Th17 cells in the tumor-infiltrating T cells in CRC patients. CRC exosomes contained abundant CRNDE-h and transmitted them to CD4(+) T cells to increase the Th17 cell proportion, ROR gamma t expression, and IL-17 promoter activity. The underlying mechanism is that, CRNDE-h bound to the PPXY motif of ROR gamma t and impeded the ubiquitination and degradation of ROR gamma t by inhibiting its binding with the E3 ubiquitin ligase Itch. The in vivo experiments confirmed that the targeted silence of CRNDE-h in CD4(+) T cells attenuated the CRC tumor growth in mice. The present findings demonstrated that the tumor exosome transmitted CRNDE-h promoted Th17 cell differentiation by inhibiting the Itch-mediated ubiquitination and degradation of ROR gamma t in CRC, expanding our understanding of Th17 cell differentiation in CRC.

Automated summary

This study found a positive correlation between serum exosomal CRNDE-h level and the proportion of Th17 cells in tumor-infiltrating T cells in CRC patients. CRNDE-h promoted Th17 cell differentiation in CRC by inhibiting Itch-mediated ubiquitination and degradation of ROR gamma t.