Fig. 4

3’UTR length change. Dynamic mRNA isoforms with differential 3’UTR are generated by APA events. This is a schematic diagram illustrating two types of 3’UTR length change. a 3’UTR shortening. Various genes possess a tendency to generate shorter mRNA isoforms in tumors than in normal tissues. With the loss of miRNA target sites, the shorter isoform will escape miRNA-mediated decay, resulting in its aberrant up-regulation. b 3’UTR lengthening. In senescent cells, many genes possess a tendency to generate longer mRNA isoforms than in normal cells. With the use of distal PASs, the longer isoforms contain more miRNA binding sites and so are more likely to be silenced. This is a suppression mechanism to reduce the expression of genes. c An example of the APA regulation mechanism. In normal liver cells, an APA regulator NUDT21, which recognizes the 2 UGUA sequences upstream of the PAS, can protect the proximal poly(A) sites from cleavage of the CPSF complex. Therefore, the expression of the target gene can be regulated by AGO2-mediated miRNA. Conversely, the expression level of NUDT21 is downregulated in HCC cells. Lacking the protection of NUDT21, the proximal PAS is more likely to be recognized and cleaved by the CPSF complex than the distal PAS. Thus, the target gene can escape from the miRNA silencing due to lack of miRNA binding sites and thus express aberrantly [9]