Conclusions
miR-216b targets CPEB4 to impair the IL-10-mediated M2 polarization of TAMs, thereby inhibiting CRC development.
Methods
The expression of genes were examined by quantitative real-time polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay and immunohistochemistry. The relationship between miR-216b and CPEB4 was verified through dual luciferase reporter assays. The proliferation, migration and invasiveness of CRC and Raw264.7 cells were assessed through cell counting kit-8 and Transwell assays. Flow cytometry was used to quantify the percentage of F4/80+/CD206+RAW264.7 cells. The metastasis of tumor cells in liver and lung tissues was evaluated by establishing a mouse xenograft tumor model and hematoxylin-eosin staining.
Results
Downregulation of miR-216b enhanced the M2 polarization of TAMs. CPEB4 was identified as a target of miR-216b. CPEB4 knockdown suppressed CRC cell proliferation, migration and invasion, which were rescued by miR-216b inhibition. It was confirmed that M2 macrophage infiltration in CRC was positively correlated with the expression levels of CPEB4 and IL-10. CPEB4 knockdown impaired the M2 polarization of Raw264.7 cells and reduced IL-10 expression. miR-216b overexpression suppressed tumor growth, metastasis and expressions of CPEB4, CD206 and IL-10 in CRC xenograft models. Conclusions: miR-216b targets CPEB4 to impair the IL-10-mediated M2 polarization of TAMs, thereby inhibiting CRC development.