Next generation sequencing analysis of drug metabolism related lncRNA in children after living donor liver transplantation

Abstract

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