For example, hypomethylation causes increased expression of mir -429 in HCC cells, and these large EVs mediated by mir -429 are shed and bind to Rb-binding protein 4 (RBBP4) in surrounding target cells, promoting the transcriptional activity of E2F1 and ultimately upregulating the expression of POU class 5 homeobox 1 (POU5F1) in target cells, thereby promoting HCC development (46). Here, RBBP4 is linked to hepatocellular carcinoma.