Exosomal circ-CTNNB1 derived from colorectal cancer cells induces N2 polarization of neutrophils to promote colorectal cancer cell growth and immune escape

[Display omitted] •Circ-CTNNB1 was first confirmed to promote CRC cell growth and immune escape.•Exosomal circ-CTNNB1 was verified to induce N2 polarization of neutrophils.•Circ-CTNNB1 was unveiled to enable neutrophils to exert cancer-promoting effect.•Circ-CTNNB1 was proved to activate NF-κB pathway via miR-3619-5p/IKBKB axis.•Circ-CTNNB1 was verified to up-regulate PD-L1 by activating NF-κB pathway. Neutrophils have been reported to promote tumorigenesis, tumor development, and immune escape. Circ-CTNNB1 has been identified as a novel tumor promoter and to be associated with the unfavorable prognosis of cancer patients. This study focused on exploring the role of circ-CTNNB1 in colorectal cancer (CRC) cell growth and its regulatory mechanism contributing to the intercellular communication between neutrophils and CRC cells. At first, circ-CTNNB1 was found to be highly expressed in CRC cells Functional assays were performed and the results indicated that silencing of circ-CTNNB1 suppressed CRC cell proliferation, accelerated cell apoptosis. After neutrophils were co-cultured with exosomes derived from CRC cells or circ-CTNNB1-silenced CRC cells, it was observed that CRC cells-derived exosomes suppressed the apoptosis of neutrophils but facilitated N2 polarization, whereas circ-CTNNB1-silenced CRC cells-derived exosomes had no significant effects on the functions of neutrophils. Mechanistic assays were conducted to explore the molecular relationships underlying circ-CTNNB1-induced CRC cell growth and immune escape. Noteworthily, circ-CTNNB1 sequestered miR-3619-5p to up-regulate IKBKB, the key factor of NF-κB signaling pathway. Moreover, circ-CTNNB1 activated NF-κB signaling pathway to increase PD-L1 expression and further stimulated N2 polarization of neutrophils, which contributed to the proliferation and immune escape of CRC cells. In summary, exosomal circ-CTNNB1 transmitted by CRC cells mediates N2 polarization of neutrophils to further promote CRC cell growth and immune escape.