miR-143-3p shuttled by M2 macrophage-derived extracellular vesicles induces progression of colorectal cancer through a ZC3H12A/C/EBPβ axis-dependent mechanism

Extracellular vesicles (EVs) exhibit pivotal functions in cancer via intercellular communication through shuttling microRNA (miRNA) and protein. Therefore, we aim to elucidate the function of EVs containing miR-143-3p derived from M2 macrophages in colorectal cancer (CRC). EVs derived from M2 macrophages were isolated and characterized. Expression changes in miR-143-3p were calculated in the EVs. The effects of M2 macrophagederived EV carrying miR-143-3p on cell biological processes and in vivo tumorigenic ability concerning ZC3H12A were examined. EVs derived from M2 macrophages could stimulate the aggressive tumor biology of CRC cells. Meanwhile, in vivo results showed that M2 macrophage-derived EVs facilitated tumor growth and epithelialmesenchymal transition. M2 macrophage-secreted EVs could transfer miR-143-3p to CRC cells, in which miR143-3p bound to the 3 ' UTR of ZC3H12A and inhibited its expression, leading to elevation of the expression of transcription factor C/EBP beta. Overall, M2 macrophage-derived EV miR-143-3p inhibits ZC3H12A gene and increases C/EBP beta expression to facilitate the development of CRC, which provides novel targets for the molecular treatment of CRC.