摘要
目的:探索LINC01419在乙肝病毒(HBV)相关性肝细胞癌(HCC)中的功能及机制。方法:分析TCGA数据库中HCC患者数据,确定LINC01419对HBV相关HCC患者的临床价值。通过荧光定量PCR检测HCC细胞中LINC01419的表达水平;检测HBx蛋白对LINC01419的表达以及LINC01419对HBV指示标志物(HBx、pgRNA、cccDNA)水平的影响。采用CCK-8实验、Transwell实验、细胞划痕实验和流式细胞术检测LINC01419对HCC细胞增殖、迁移和侵袭的影响。结果:LINC01419对HBV相关性HCC患者生存期有显著影响。LINC01419在HBV阳性的HepG2.215细胞中的表达高于HBV阴性的HepG2细胞;并且在产生HBV的HepAD38细胞和感染HBV后的HepG2-NTCP细胞中,LINC01419的表达水平显著提高。在细胞中过表达HBx蛋白可以显著提高LINC01419的表达量;提高LINC01419水平可以提高HepG2.215细胞中HBV相关性标志物HBx、pgRNA、cccDNA的水平。过表达LINC01419可促进HCC细胞的增殖、迁移和侵袭,并且在HepG2.215细胞和HepAD38(HBV阳性)细胞中的促进作用较HepG2和HepAD38(HBV阴性)细胞更加显著。结论:LINC01419可激活HBV的复制,同时LINC01419和HBV协同作用促进了HBV相关HCC的恶性进展。
Objective:To explore the function and mechanism of LINC01419 in hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods:Analysis of HCC patient data from the TCGA database to determine the clinical value of LINC01419 in patients with HBV-related HCC.The expression level of LINC01419 in HCC cells was assessed using real-time quantitative reverse PCR(qRT-PCR).The impact of HBx protein on LINC01419 expression and the effects of LINC01419 on HBV indicator markers(HBx,pgRNA,cccDNA)were investigated.Various assays including CCK-8,Transwell,cell scratch,and flow cytometry were employed to assess the effects of LINC01419 on cell proliferation,migration and invasion in HCC cells.Results:LINC01419 had a significant effect on the survival of patients with HBV-associated HCC.The expression of LINC01419 was higher in HBV-positive HepG2.215 cells than in HBV-negative HepG2 cells.Moreover,in HBV-producing HepAD38 cells and HepG2-NTCP cells after infection with HBV,LINC01419 expression levels were significantly increased.Overexpression of HBx protein in cells significantly increased the expression of LINC01419.Increasing the level of LINC01419 increased the levels of HBV-associated markers HBx,pgRNA,and cccDNA in HepG2.215 cells.Overexpression of LINC01419 promoted the proliferation,migration,and invasion of HCC cells,and the promotion was more pronounced in HepG2.215 cells and HepAD38(HBV-positive)cells than in HepG2 and HepAD38(HBV-negative)cells.Conclusion:LINC01419 activates HBV replication,while LINC01419 and HBV synergistically promote the malignant progression of HBV-associated HCC.
作者
万美玲
李德成
孙长峰
刘晓玲
盛云建
李亚玲
邓存良
WAN Meiling;LI Decheng;SUN Changfeng;LIU Xiaoling;SHENG Yunjian;LI Yaling;DENG Cunliang(Department of Infectious Diseases,the Affiliated Hospital of Southwest Medical University,Laboratory of Infection and Immunology,Sichuan Luzhou 646000,China;Department of Pharmacy,the Affiliated Hospital of Southwest Medical University,Sichuan Luzhou 646000,China)
出处
《现代肿瘤医学》
CAS
2024年第21期4035-4043,共9页
Journal of Modern Oncology
基金
四川省科技厅资助项目(编号:2022YFS0625)。
