HBV感染对肝癌细胞脂类代谢相关蛋白表达的影响

Effects of HBV infection on lipid metabolism-related protein expression in hepatocellular carcinoma cells

乙型肝炎病毒(hepatitis B virus,HBV)是非细胞病变的病毒,其持续感染造成的肝脏损伤逐步引起肝脏炎症,进而导致肝纤维化、肝硬化,最终引发了80%的肝细胞肝癌(hepatocellular carcinoma,HCC)。肝脏是机体代谢的重要器官,癌基因的异常活化以及抑癌基因的抑制失活会造成细胞代谢水平以及代谢方式的改变,此过程被称为细胞代谢重编程(metabolism reprogramming),代谢重编程是肝脏炎症向癌症转化的关键步骤。本研究通过逆转录聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)、酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)、多重荧光免疫组化等方法检测HBV阳性细胞(或组织)与对照细胞(或组织)中脂质代谢关键基因的表达,在此基础上分析其功能和脂代谢的关系。结果显示,在稳定表达HBV的HepG2.2.15及HBsAg的Hep3B细胞中,脂代谢相关基因HMGCR、SREBP-2以及PSCK9的mRNA表达量显著上调,且在肝细胞癌患者的临床病理结果中相应蛋白表达水平也同步提高,提示HBV感染导致了相应代谢基因的高表达,且HBsAg是调控脂质代谢酶基因紊乱的关键蛋白。通过分析365例大样本肝癌患者的病理资料,本文发现脂代谢相关基因在肝癌组织中的高表达有预后变差的趋势,提示脂质代谢的紊乱可能是影响肝癌患者总生存期的危险因素。

Hepatitis B virus(HBV)is a non-cytopathic virus,and the liver damage caused by its continuous infection gradually causes liver inflammation,which leads to liver fibrosis,cirrhosis,and eventually causes 80%of hepatocellular carcinoma(HCC).Liver is an important organ of metabolism in the body.The abnormal activation of oncogenes and the inactivation of tumor suppressor genes will cause changes in the level and mode of cell metabolism,which is called metabolism reprogramming.Metabolic reprogramming is a key step in the transformation from liver inflammation to cancer.In this study,the expressions of key genes of lipid metabolism in HBV-positive cells(or tissues)and control cells(or tissues)were detected by reverse transcription-polymerase chain reaction(RT-PCR),enzyme linked immunosorbent assay(ELISA)and multiple fluorescence immuno histochemistry,and on this basis,the relationship between their functions and lipid metabolism was analyzed.The results showed that in HepG2.2.15 cells with stable HBV expression and Hep3B cells with stable HBsAg expression,the mRNA expressions of lipid metabolism-related genes HMGCR,SREBP-2 and PSCK9 were significantly up-regulated,and the corresponding protein expression levels were also increased synchronously in the clinicopathological results of hepatocellular carcinoma patients.It is suggested that HBV infection leads to the high expression of corresponding metabolic genes,and HBsAg is the key protein regulating the disorder of lipid metabolism enzyme genes.By analyzing the pathological data of 365 large samples of liver cancer patients,it was found that the high expression of lipid metabolism-related genes in liver cancer tissues has a trend of poor prognosis,suggesting that the disorder of lipid metabolism may be a risk factor affecting the overall survival of liver cancer patients.