摘要
目的用高通量二代测序(nextgenerationsequencing, NGS)分析儿童肝移植供肝标本的长链非编码RNA(lncRNAs)及mRNA的表达情况,寻找差异表达的lncRNA以及药物代谢基因mRNA,为儿童肝移植免疫抑制剂个体化指导提供依据。方法收集2016年10月至2017年12月亲属活体肝移植的供肝组织标本10例,根据术后药物代谢情况分为快代谢和慢代谢两组(各5例),进行mRNA和lncRNA高通量测序。对差异基因进行功能通路分析,并通过靶基因预测筛选关键基因。结果慢代谢组与快代谢组中有908个mRNA和1 228个lncRNA的表达差异有统计学意义(P<0.05),其中表达丰度高且差异显著的药物代谢相关mRNA有40个,22个上调,18个下调;lncRNA 有37个,13个上调,24个下调。除经典药物代谢相关基因CYP3A5之外,我们还发现CYP2C19、CYP1A2、UGT1A1可能对他克莫司的代谢产生影响作用。同时lncRNA中NONH-SAT108 617. 2可能靶向调节CYP3A5基因的表达。结论本研究全面分析了儿童亲属活体肝移植供肝标本中lncRNA及mRNA的表达特征,其中一些差异的药物代谢相关基因可能共同作用影响他克莫司体内代谢,进而对术后免疫抑制剂用药产生影响。
Objective To employ high-throughput next generation sequencing (NGS) for analyzing the expression of lncRNAs and mRNAs in donor samples from pediatric living donor liver transplantation and search differentially expressed lncRNAs and drug metabolic gene for individualized guidance of immunosuppressive agents. Methods Between October 2016 and December 2017, 10 liver tissue specimens from living donor liver transplantation children were collected and divided into fast and slow metabolic groups (72 = 5 each) according to the postoperative profiles of drug metabolism. Samples were assayed for high- throughput NGS Target analysis was used for functional pathways and screening target genes prediction. Results There were differentially expressed 908 mRNAs and 1228 lncRNAs between slow metabolic and fast metabolic groups (P<0. 05). According to the abundance and difference 22 up-regulated and 18 down- r^ulated mRNAs, 13 up-regulated and 24 down-regulated lncRNAs were selected. In addition to CYP3A5, CYP2C19, CYP1A2 and UGT1 Al might affect the metabolism of tacrolimus. At the same time, NONHSAT108617. 2 in differentially expressed lncRNAs might regulate the expression of CYP3A5 gene. Conclusions This study has comprehensively analyzed the expression of lncRNAs in donor liver from pediatric liver transplantation. Some differentially expressed drug metabolism related genes may affect tacrolimus metabolism in vivo and thus the postoperative use of immunosuppressive drugs.
作者
秦天
顾向前
郑建新
刘金川
唐元家
薛峰
夏强
Qin Tian;Gu Xiangqian;Zheng Jianxin;Liu Jinchuan;Tang Yuanjia;Xue Feng;Xia Qiang(Department of Liver Surgery, Affiliated Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China)
出处
《中华器官移植杂志》
CAS
北大核心
2019年第4期219-225,共7页
Chinese Journal of Organ Transplantation
基金
国家自然科学基金(81670602).
关键词
肝移植
长链非编码RNA
药物代谢
Liver transplantation
Long noncoding RNA
Drug metabolism
