Circular RNA FMN2 motivates colorectal cancer development by mediating tumor-associated macrophage polarization by controlling the microRNA-150-5p/PIK3R3 axis

Background

It has been reported that circular RNA formin 2 (circFMN2) can motivate colorectal cancer (CRC) proliferation. However, the effect of circFMN2 on the polarization of tumor-associated macrophages (TAMs) in the CRC tumor microenvironment remains unclear. The study was to figure out the latent mechanism by which circFMN2 impacts TAM polarization to motivate the malignant behavior of CRC cells.

Results

circFMN2 and PIK3R3 levels were reduced in M1 macrophages but elevated in M2 macrophages, whereas miR-150-5p level was the opposite. circFMN2 knockdown downregulated M2 macrophage markers CD163, CCL22 and CD206 and upregulated M1 macrophage markers CD86, TNF-α and IL-1β in M2 macrophages. Co-culture with M2 macrophage-conditioned medium with circFMN2 knockdown reduced CRC proliferation, invasion, and migration, while knockdown of miR-150-5p had the opposite effect. CircFMN2 adsorbed miR-150-5p to mediate PIK3R3 in M2 macrophages. Overexpression of miR-150-5p can reverse the promoting effects of overexpression of circFMN2 on M2 polarization, CRC cell proliferation, invasion, and migration. Elevation of PIK3R3 could turn around the repressive effect of circFMN2 knockdown on M2 polarization and CRC cell proliferation, invasion, and migration. In an in vivo model, M2 macrophages expressing low or high circFMN2 were co-transplanted with CRC cells into nude mice, resulting in inhibition and promotion of tumor growth, respectively.

Conclusions

All in all, circFMN2 mediates TAM polarization to M2 type by controlling the miR-150-5p/PIK3R3 axis to motivate CRC development and may offer a latent molecular target for CRC treatment.

How to cite: Cao Y, Cao D, Zhu T. Circular RNA FMN2 motivates colorectal cancer development by mediating tumor-associated macrophage polarization by controlling the microRNA-150-5p/PIK3R3 axis. Electron J Biotechnol 2024;68. https://doi.org/10.1016/j.ejbt.2023.12.002.