E2F1 and hepatocellular carcinoma: On the other hand, some up-regulated transcription factors (e.g. E2F1 and FOXM1) can activate multiple carcinogenic miRNAs (e.g. miR-21-5p and miR-96-5p) to inhibit FOXO1 to lead to the disorder of FOXO1-miRNA-PI3K/RAS/ERK cancer suppressive feedback loop to cause the occurrence and development of HCC (Figure 6).