fig4

Figure 4. Theoretical framework of Cancer Evo-Dev, as exampled by HBV-induced hepatocarcinogenesis. A: The classic diagram of Cancer Evo-Dev. The imbalance between mutation-promoting forces like AID/APOBECs and mutation-repairing forces like UNGs is responsible for the generation of somatic and viral mutations; B: exposures to some mutagens and HBV infection lead to mitochondria DNA mutations, thus promoting Warburg effect. In addition, AID/APOBECs also demethylates the promoters regions of some transcriptional factors including, thus directly promoting EMT; C: the diagram of Cancer Evo-Dev explaining why HCC is a male sex-predominant cancer. mtDNA: mitochondria DNA; AID/APOBECs: activation-induced cytidine deaminases/the human apolipoprotein B mRNA-editing enzyme catalytic polypeptide; UNG: uracil DNA glycosylase; EMT: epithelial-mesenchymal transition; HBV: hepatitis B virus; AR: androgen receptor; ROS: reactive oxygen species; Mt: mitochondria; HCC: hepatocellular carcinoma