It was found that sEVs derived from highly metastatic CRC cells enriched in miR-181a-5p-activated hepatic stellate cells (HSCs) by activating the IL6/STAT3 signaling pathway, acting directly on suppressor of cytokine signaling 3 (SOCS3) and causing TME remodeling. The gene discussed is IL6; the disease is colorectal carcinoma.