Editor's note:The 74th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2023) was held in Boston, USA from November 10 to 14, 2023 local time.
At present, the disease burden of liver cancer in China is still relatively severe, of which 86%-92% is caused by hepatitis B. Therefore, it is extremely important to understand the relevant mechanism of HBV leading to liver cancer, which can provide an effective way for the prevention and development of liver cancer.
Recently, Professor Tang Hong, Professor Cao Dan and Professor Chen Han from West China Hospital of Sichuan University published a study on the angiogenic mechanism of HBV-related liver cancer in the abstract of the AASLD 2023 conferenceHepatitis B virus-encoded microRNA 3 (HBV-miR-3) by targeting FIH-1 mRNA3'-UTR, which promotes the angiogenesis signaling pathway, thereby regulating the angiogenesis of HBV-related hepatocellular carcinoma.
Background:HBV cccDNA can generate microRNAs that bind to target mRNA to inhibit post-transcriptional gene expression. The hepatitis B virus-encoded microRNA 3 (HBV-miR-3) regulates HBV replication and host gene expression in hepatocellular carcinoma. Hypoxia-inducible factor 1 (HIF-1) inhibitor (FIH-1), also known as hypoxia-inducible factor 1 inhibitory protein (HIF1AN), hydroxylates HIF-1 to inhibit transcription of vascular endothelial growth factor A (VEGFA). 1 of FIH-3'-UTR has a target sequence of HBV-MIR-3.
Research Methods:The expression of HBV-Mir-3 in HBV-related HCC tissues was detected by stem-loop qPCR and survival analysis was performed. qPCR was used to detect the expression of VEGFR2 in liver cancer tissues, and its correlation with HBV-MIR-3 was analyzed.
HEPG2 cells were transfected with HBV-Mir-3 agonist and HEPG2 with HBV-miR-3 antagonist2.15 cells, and the expression levels of FIH-1, HIF-1 and VEGFA were detected. Establish hepg2 hepg22.15. Co-culture model with human umbilical vein endothelial cells (Huvec) for analysis of HEPG2 cells transfected with HBV-Mir-3 agonists or HEPG2 transfected with HBV-Mir-3 antagonists2.Effect of 15 cells on HUVEC vascularization.
Verification of HBV-miR-3 targeting FiH-1 mRNA 3 by luciferase reporter system'-Binding sites and nucleic acid sequences of UTR. HEPG2 and HEPG2 are used2.A mouse tumor-bearing model was established with 15 cells, and HBV-Mir-3 agonists and antagonists were injected into tumors, and the expressions of FIH-1, HIF-1, VEGFA and VEGFR2 were analyzed.
Findings:The expression of HBV-mir-3 was significantly correlated with the angiogenesis-related genes VEGFR2 and FIH-1These results suggest that HBV-miR-3 may be involved in the angiogenesis of HBV-related hepatocellular carcinoma.
In vitro experiments, HBV-MIR-3 agonists inhibited the expression of FIH-1 in hepatoma cells, promoted the expression of HIF-1 and VEGFA, and led to an increase in the formation of the lumen of HUVECHBV-miR-3 antagonists induce the expression of FIH-1 in hepatoma cells and inhibit the expression of HIF-1 and VEGFA, resulting in a decrease in the formation of Huvec lumen. The results show that:HBV-MIR-3 regulates angiogenesis in HBV-associated hepatocellular carcinoma by upregulating the expression of HIF-1 VEGFA.
HBV-miR-3 vs. Fih-1 mRNA 3'The binding site of -UTR was confirmed by luciferase activity assay. The role of HBV-miR-3 in regulating tumor angiogenesis has also been demonstrated in a tumor-bearing mouse model. These data show thatHBV-miR-3 by targeting FIH-1 mRNA3'-UTR, which promotes the angiogenesis signaling pathway, thereby regulating the angiogenesis of HBV-related hepatocellular carcinoma.
Conclusions of the studyHBV-MiR-3 promotes angiogenesis in HBV-associated HCC by inhibiting post-transcriptional expression of FIH-1, which may be a novel mechanism by which HBV promotes angiogenesis in HBV-associated HCC.
Liver Linjun has something to sayWith the deepening of basic research, the mechanism of HBV leading to liver cancer has been understood. This study also showed that HBV-miR-3 produced by HBV cccdna can promote the angiogenesis signaling pathway by targeting FIH-1 mRNA, thereby regulating the angiogenesis of HBV-related liver cancer. It can be seen that cccdna clearance may be effective in reducing the risk of liver cancer in patients with chronic hepatitis B. Previous studies have shown that the intrahepatic cccdna level in patients with chronic hepatitis B is significantly reduced after obtaining clinical **, and 27% of these patients have achieved cccdna clearance. Therefore, patients with chronic hepatitis B should pursue clinical practice as soon as possible to reduce the impact of HBV on the liver and minimize the risk of liver cancer.
References:
chen h, tang h, cao d. hepatitis b virus-encoded microrna (hbv-mir-3) inhibits fih-1 expression to promote tumor angiogenesis in hbv-related hepatocellular carcinoma. aasld2023, abstract (1503-c).
Hepatitis B