In addition, HCC cells secreted exosomal miRNA-21 that directly targeted PTEN, leading to activation of pyruvate dehydrogenase kinase 1 (PDK1)/AKT signaling in HSCs; then promoted cancer progression by secreting angiogenic cytokines, including vascular endothelial growth factor (VEGF), matrix metallopeptidase 2 (MMP2), MMP9, basic fibroblast growth factor (bFGF), and transforming growth factor-β (TGF-β) (69). This evidence concerns the gene MMP2 and hepatocellular carcinoma.