高氨诱导的肝细胞中凋亡相关LncRNA表达谱的变化

Changes of apoptosis-related LncRNA expression profiles in hyperammonemia-induced hepatocytes

目的:探讨高氨诱导的肝细胞中凋亡相关长链非编码RNA(LncRNA)表达谱的变化。方法:将人正常肝细胞LO2细胞分为3组,对照组常规培养,高氨1组、高氨2组分别用10 mmol/L氯化铵溶液诱导24、48 h,以制备高氨肝细胞模型。应用人凋亡通路LncPathTM芯片筛选3组肝细胞差异表达的LncRNA和mRNA,并进行GO注释和KEGG通路分析,使用Cytoscope构建ceRNA网络图。结果:3组间差异表达的LncRNA有8个,差异表达的mRNA有13个。GO注释和KEGG通路分析结果显示,差异表达LncRNA及mRNA主要参与的信号通路有孕激素介导的卵母细胞成熟通路、神经营养因子信号通路、卵母细胞减数分裂和MAPK信号通路;ceRNA网络分析结果提示MAPK12是LncRNA BAIAP3的靶基因。结论:LncRNA BAIAP3可能通过靶向MAPK12在高氨致肝细胞凋亡过程中发挥重要作用。

Aim:To investigate the changes of expression profile of apoptosis-related long non-coding RNA(LncRNA)in hyperammonemia induced hepatocytes.Methods:Human normal hepatocyte LO2 cells were allocated into three groups.Control group was cultured normally.Hyperammonemia 1 group and hyperammonemia 2 group were induced with 10 mmol/L ammonium chloride solution for 24 hours and 48 hours,respectively,to prepare hyperammonemia hepatocyte model.The differential expressing LncRNA and mRNA in hepatocytes of the three groups were screened by LncPathTM array and analyzed by GO annotation and KEGG,and ceRNA network was constructed by Cytoscope.Results:There were 8 dysregulated LncRNA and 13 dysregulated mRNA among the 3 groups.GO and KEGG analysis showed that these dysregulated LncRNA and mRNA mainly involved four signal pathways(the progesterone-mediated oocyte maturation pathway,the neurotrophin pathway,the oocyte meiosis and the MAPK pathway),the results of ceRNA network analysis suggested that MAPK12 was the target gene of LncRNA BAIAP3.Conclusion:LncRNA BAIAP3 may play an important role in hyperammonemia-induced hepatocyte apoptosis process through targeting MAPK12.