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乙型肝炎病毒(hepatitis B virus,HBV)X蛋白(HBx)对肝癌的发生发展具有十分重要的作用.我们前期研究发现,HBx突变体(HBxΔ127)与肝癌的增殖和迁移有密切的关系.钙蛋白酶小亚基1(calpain small subunit 1,Capn4)具有促进细胞迁移、增殖和分化的作用.本研究对HBx突变体(HBxΔ127)促进肝癌细胞迁移的分子机制进行了研究.实验结果显示,HBxΔ127可明显激活Capn4的启动子活性和上调Capn4蛋白表达.应用ERK抑制剂PD98059作用肝癌细胞后,可明显抑制HBxΔ127对Capn4的上调作用,提示HBxΔ127可通过磷酸化ERK1/2(p-ERK1/2)上调Capn4.应用伤口愈合实验进一步证实,HBxΔ127促进肝癌细胞迁移的作用与Capn4和p-ERK1/2有关.本研究结果表明,HBxΔ127促进肝癌细胞迁移的作用是通过p-ERK1/2上调Capn4实现的.这一发现对进一步揭示HBx突变体HBxΔ127促进肝癌细胞转移的分子机制具有重要意义.
Hepatitis B virus (HBV) X protein (HBx) plays a very important role in the development of liver cancer.Our previous study found that the HBx mutant (HBxΔ127) is closely related to the proliferation and migration of liver cancer.Calcium The effect of HBx mutant (HBxΔ127) on the migration of hepatocarcinoma cells was studied in this study.The results showed that the expression of HBxΔ127 Significantly activated Capn4 promoter activity and up-regulated Capn4 protein expression.Expression of Capx4 was up-regulated by PD98059, a potent inhibitor of HBxΔ127, suggesting that HBxΔ127 may be up-regulated by phosphorylation of ERK1 / 2 (p-ERK1 / 2) The effect of HBxΔ127 on the migration of hepatocellular carcinoma cells was also related to Capn4 and p-ERK1 / 2. The results of this study indicated that the effect of HBxΔ127 on the migration of hepatocellular carcinoma cells was through the up-regulation of Capn4 by p-ERK1 / 2. This finding is of great significance for further revealing the molecular mechanism of HBxΔ127 promoting the metastasis of hepatoma cells.