Functional analysis of hepatic long non-coding RNAs during liver transplantation in human.

Abstract

The potential function of lncRNAs in human hepatic ischemia reperfusion injury (HIRI) remains to be clarified. Clinical samples of transplanted liver tissues from 26 patients undergoing liver transplantation (LT) and normal liver tissues from 7 patients undergoing hepatic hemangiomactomy (Con) were collected. Typical samples were subjected to whole-transcriptome sequencing (RNA-seq). Differentially expressed genes between groups were identified by DEGseq and were analyzed by enrichment analysis including GO, KEGG and GSEA. Transcription of 5 lncRNAs including NONHSAG039942, NONHSAG071405, NONHSAG027516, LXLOC_058190 and LXLOC_024376 that presented significant difference in RNA-seq were validated by qRT-PCR, whose subcellular localization and the binding ability to known human RNA binding proteins (RBPs) were respectively predicted by LncLocator and catRAPID genomics v2.1. We identified 2917 lncRNAs and 2811 mRNAs that were differentially expressed (p < 0.05 and log2 Fold Change > 1 or < -1) between groups (LT vs. Con). NONHSAG039942, NONHSAG071405, LXLOC_058190 and LXLOC_024376 were validated by qRT-PCR to be significantly increased in LT group, and were all predicted to be localized in cytoplasm or cytosol. NONHSAG039942, NONHSAG071405, and LXLOC_058190 held an RBP interaction propensity score of 98.07%, 76.95%, and 152.99%, respectively, with Heterogeneous-Nuclear Ribonucleoprotein U (HNRNPU). Pathways significantly activated in transplant livers that involved HNRNPU as a core enrichment gene included hypoxia, ACE2 expression, apoptosis, spliceosome formation, etc. CONCLUSIONS: NONHSAG039942, NONHSAG071405 and LXLOC_058190 significantly increased in transplant livers after reperfusion and their role in HIRI may be associated with HNRNPU, a core protein that participates in hypoxia and chromatin accessibility.