Autophagy and microRNA in hepatitis B virus-related hepatocellular carcinoma

Figure 1 How hepatitis B virus infection induces autophagy. Hepatitis B virus (HBV) induces autophagy mainly through HBx protein or small surface protein (Small HBs)-related mechanism. The former (HBx) induces autophagy by the following routes: (1): Increases mRNA expression of Beclin 1 through transcriptional regulation; (2): Activates enzymatic activity of PI3KC3 to enhance autophagosome formation; (3): Activates DAPK to trigger autophagy in a Beclin 1-PI3KC3-dependent manner. The latter (SHBs) triggers ER stress to induce autophagy. DAPK: Death-associated protein kinase.

Figure 2 The relationship between hepatitis B virus-induced autophagy and hepatitis B virus replication. Hepatitis B virus (HBV)-induced autophagy regulates virus replication and maturation at different stages of HBV replication. (I): Autophagy enhances HBV replication at the DNA replication stage; (II): HBV-induced autophagy is required for viral envelopment. However, envelope proteins (HBs) could be eliminated via the autophagic degradation pathway (III).

Figure 3 Hepatitis B virus affects microRNA transcription and stability. Hepatitis B virus (HBV) suppresses miR-122 through different mechanisms. A: HBV suppresses miR-122 promoter activity and expression through transcriptional regulation by directly interacting with peroxisome proliferator activated receptor-gamma (PPARγ); B: HBx suppresses transcription of Gld2 to decrease miR-122 stability; and C: HBV functions as a sponge to bind miR-122 and reduces its expression. RXRa: Retinoid X Receptor, Alpha; Gld2: Germline development 2.

Figure 4 Hepatitis B virus regulates microRNAs biogenesis. Hepatitis B virus (HBV) regulates the biogenesis of miRNA by affecting the miRNA-related Rnases. HBx protein downregulates Drosha expression through reduction of the transcriptional activity of Drosha promoter and upregulates the expression of transcription factor YY1 to suppress DGCR8 expression by repressing DGCR8 promoter activity. Single nucleotide polymorphisms (SNPs) located on 3’UTR of Dicer and RAN genes affect the biogenesis of miRNA in HBV-related diseases. DGCR8: DiGeorge syndrome critical region gene 8.