Whole transcriptome analysis reveals that immune infiltration- lncRNAs are related to cellular apoptosis in liver transplantation

Shile Wu; Chao Cheng; Wenjun Zhu; Jinyu Yang; Bei-Bei He; Song Li; Xinsheng Wang; Hao Guo; Dong Chen; Ya-Min Guo

doi:10.3389/fimmu.2023.1152742

Whole transcriptome analysis reveals that immune infiltration- lncRNAs are related to cellular apoptosis in liver transplantation

Front Immunol. 2023 Apr 4:14:1152742. doi: 10.3389/fimmu.2023.1152742. eCollection 2023.

Authors

Shile Wu^{1

2}, Chao Cheng³, Wenjun Zhu², Jinyu Yang², Bei-Bei He², Song Li², Xinsheng Wang², Hao Guo³, Dong Chen³, Ya-Min Guo²

Affiliations

¹ Soochow University, Suzhou, Jiangsu, China.
² General Surgery Department, Qinghai Provincial People's Hospital, Xining, Qinghai, China.
³ Center for Genome Analysis, Wuhan Ruixing Biotechnology Co., Ltd, Wuhan, China.

Abstract

Introduction: In most instances, liver transplantation (LT) is the only available treatment for end-stage liver diseases. However, LT could also induce serious liver diseases or injury, and the underlying mechanisms of LT-induced complications remain largely unknown, especially the mechanisms of the dysfunction of the immune system mediated by long noncoding RNAs (lncRNAs).

Methods: In this study, we globally analyzed the proportion of immune cells by using the transcriptome sequencing data (RNA-seq) of needle-core liver biopsies from pre- and post-transplantation recipients. Dysregulated lncRNAs were found to be correlated with the altered fractions of immune cells. We finally explored the potential targets of dysregulated lncRNAs and analyzed their functions in LT.

Results: We found that in the samples, some immune cells changed significantly after LT, including CD4 T cells, NK cells and mast cells. The proportion of macrophages in different polarization states also changed significantly, with M0 macrophages increasing and M2 macrophages decreasing. Through weighted gene co-expression network analysis (WGCNA), 7 gene expression modules related to LT were identified. These modules were related to changes in the proportion of different immune cells. The functions of these modules represent the response modes of different functional genes after LT. Among these modules, MEtan and MEyellow modules were primarily enriched in apoptosis and inflammatory pathways. Twelve immunity-related lncRNAs were identified for the first time, and the regulatory network co-changing with immune cells was also identified. The co-expressed genes of these lncRNAs were highly enriched in apoptosis-related pathways. Many apoptosis-related genes were found to be up-regulated after LT.

Discussion: In summary, we speculated that the expression and regulation of these apoptotic genes may be related to the changes in the proportion of immune cells. Some of these lncRNAs and apoptosis-related genes have been reported to be related to cell proliferation and apoptosis. They are also potential biomarkers or therapeutic targets.

Keywords: apoptosis; co-expression; immune cells; liver transplantation; lncRNAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / genetics
Gene Expression Profiling
Liver Transplantation* / adverse effects
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Transcriptome

Substances

RNA, Long Noncoding

Grants and funding

This work was supported by Qinghai Sciences and Technology Department for Basic Research Program (2020-ZJ-770) and a grant from Key Construction Project of Qinghai Provincial Health Commission, Organ Transplantation.