儿童活体肝移植后药物代谢相关lncRNA的下一代测序分析

Tian Qin, Xiangqian Gu, J. Zheng, Jinchuan Liu, Yuanjia Tang, F. Xue
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引用次数: 0

摘要

目的应用高通量下一代测序(NGS)技术分析儿童活体肝移植供体样本中lncRNAs和mrna的表达,寻找差异表达的lncRNAs和药物代谢基因,为免疫抑制剂的个体化指导提供依据。方法于2016年10月至2017年12月收集10例活体供肝移植患儿肝组织标本,根据患儿术后药物代谢情况分为快代谢组和慢代谢组,每组5例。对样品进行高通量NGS检测。靶标分析用于功能通路和筛选靶基因预测。结果慢代谢组与快代谢组mrna和lncrna的表达差异有908个,lncrna的表达差异有1228个(P<0.05)。根据丰度和差异,我们选择了22个上调mrna和18个下调mrna, 13个上调lncrna和24个下调lncrna。除CYP3A5外,CYP2C19、CYP1A2和UGT1A1也可能影响他克莫司的代谢。同时,差异表达lncRNAs中的NONHSAT108617.2可能调控CYP3A5基因的表达。结论本研究全面分析了小儿肝移植供肝中lncRNAs的表达。一些差异表达的药物代谢相关基因可能影响他克莫司体内代谢,从而影响术后免疫抑制药物的使用。关键词:肝移植;长链非编码RNA;药物代谢
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Next generation sequencing analysis of drug metabolism related lncRNA in children after living donor liver transplantation
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 (n=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-regulated mRNAs, 13 up-regulated and 24 down-regulated lncRNAs were selected. In addition to CYP3A5, CYP2C19, CYP1A2 and UGT1A1 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. Key words: Liver transplantation; Long noncoding RNA; Drug metabolism
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