Hepatic Stellate Cells Inhibit Epithelial-to-Mesenchymal Transition of Hepatoma Cells: Effect of MiR-233 Modification on Exosomes

摘要

Hepatic stellate cells (HSCs) dominate the malignant microenvironment that induces metastasis related epithelial-to-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC). Here, we employed miR-223 to modify the activated HSCs. HSC-secreted exosomes were integrated to hepatoma cells (HepG2 and Huh7). Dramatic increase in exosomal miR-223, and then intracellular miR-223 in both types of cells revealed the transcellular delivery of miRNA. The miR-223-specific inhibitory effect on Sp1 abolished mesenchymal markers (N-cadherin, Vimentin), and rescued epithelial marker of E-cadherin. Wound healing and transwell assay exhibited the amelioration of invasion in hepatoma cells. These findings highlight the exosome-mediated regulation of miRNA by HSCs modification, which renders a potential therapy for HCC based on EMT attenuation.