MiR-302 a/b/c suppresses tumor angiogenesis in hepatocellular carcinoma by targeting MACC1.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a hypervascularized tumor. Aberrant angiogenesis is the main cause, which results in cancer growth and progression. It has been showed that microRNA-302 cluster (miR-302) may be associated with angiogenesis. Here, we aimed to identify the role of miR-302a/b/c in the regulation of cell angiogenesis in HCC. PATIENTS AND METHODS: MRNA expression of miR-302a/b/c and MACC1 was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The protein of MACC1 was measured using Western blot. Cells proliferation, migration, and invasion abilities were investigated via Cell Counting Kit-8 (CCK-8) assay or transwell assay, respectively. Tube formatting assays were used to explore the tube formation capacity. The interaction among miR-302a/b/c was analyzed by luciferase assay. RESULTS: The expression of miR-302a/b/c was greatly reduced while MACC1 expression, whether mRNA or protein was conspicuously elevated in HCC tissues and cells. Then, functional experiment results showed miR-302a/b/c overexpression and MACC1 down-regulation inhibited the proliferation, migration, invasion ability, and tube formation capacity of HUVECs. In addition, we detected that miR-302a/b/c directly targeted MACC1 and suppressed MACC1 expression, and miR-302a/b/c could suppress tumor angiogenesis in HCC by targeting MACC1. CONCLUSIONS: MiR-302a/b/c may function as a potential suppressor of tumor angiogenesis in HCC by targeting MACC1, indicating a promising target for HCC therapy.

[Qualitative pathological assessment of liver fibrosis regression after antiviral therapy in patients with chronic hepatitis B].

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion: This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.