| Mechanisms of HBx-induced hepatocarcinogenesis |
| Regulatory noncoding RNAs |
| miRNAs |
| miR-148a activates mTOR11
|
| miR-15b increases the levels of Globo H12
|
| miR-205 increases the expression of ACSL1 and triglyceride13,14
|
| miR-224 silences Smad415
|
| lncRNAs |
| HULC suppresses the expression of p1816
|
| Dreh represses the expression of intermediate filament protein vimentin17
|
| Epigenetic modification |
| Methylation |
| Upregulates the expression of DNMT1 and DNMT3A21-23
|
| Acetylation |
| Induces the expression of HDAC124-26
|
| Upregulates SIRT128,29
|
| Functions of HBx in HBx-related hepatocarcinogenesis |
| Signaling pathway |
| Akt |
| Stabilizes β-catenin32
|
| Promotes IKKα nuclear translocation33
|
| Wnt |
| Hyperactivates the transcription of cyclin D, VEGF, c-MYC, and AR36,37,64
|
| Stat |
| Activates the Twist promoter39,40
|
| NF-κB |
| Upregulates the heat shock protein gp9641
|
| Enhances the expression of IKKα42,43
|
| Cell transformation |
| Exerting strong growth arrest and imbalanced cell-cycle progression45-47
|
| Apoptosis |
| Caspases |
| Inhibit Notch signaling49
|
| Accelerate the loss of Mcl-1 protein50
|
| Mitochondria |
| Stimulate the mitochondrial translocation of Raf-151
|
| Induce the perinuclear clustering of the mitochondria52
|
| Increase the mitochondrial calcium uptake53
|
| PDCD4 |
| Induce TGF-β1-mediated apoptosis9,55
|
| Immune system |
| Innate immune |
| Prevent the induction of IFN-β58,59
|
| Adaptive immunity |
| Accumulate CD8+ T cells62
|
