# Comprehensive characterization of the competitive endogenous RNA network revealing its immune-related functions in hepatic ischemia-reperfusion injury

**Authors:** Lirong Liu, Qi Wang, Shuang Qin, Chang Su, Xin Hai, Zhenkuan Yuan

PMC · DOI: 10.1371/journal.pone.0327101 · PLOS One · 2025-07-24

## TL;DR

This study identifies a ceRNA network in liver injury that influences immune responses, potentially offering new therapeutic targets.

## Contribution

The paper presents a novel immune-related ceRNA subnetwork and axis in hepatic ischemia-reperfusion injury.

## Key findings

- A ceRNA network involving 3 lncRNAs, 3 miRNAs, and 29 mRNAs was identified in liver transplant patients.
- The PARD6G-AS1/miR-125b-5p/IL24 axis may influence NK cell activity in HIRI.
- The ceRNA network regulates immune-related pathways and immune cell infiltration in HIRI.

## Abstract

Hepatic ischemia-reperfusion injury (HIRI) is a common complication in liver surgery and transplantation. Recent studies have revealed the significant role of the competing endogenous RNA (ceRNA) network in HIRI. Herein, we comprehensively analyzed the HIRI-related ceRNA network and its correlation with immune-related pathways and immune cells in HIRI patients. We identified 449 lncRNAs, 26 miRNAs, and 548 mRNAs differentially expressed in HIRI patients. We constructed a HIRI-related ceRNA network in liver transplant patients consisting of 3 lncRNAs, 3 miRNAs, and 29 mRNAs. Biological function analysis showed that the HIRI-related ceRNA network contributes to HIRI progression by regulating calcium ion-related regulatory pathways and processes. An immune-related ceRNA subnetwork, which consists of 1 lncRNA (PARD6G-AS1), 1 miRNA (hsa-miRNA-125b-5p), and 4 mRNAs (PLAU, CCR5, FGF5 and IL24) was obtained. The immune-related ceRNA subnetwork was significantly related to the immune-related pathways and immune cell infiltration. The PARD6G-AS1/miR-125b-5p/IL24 axis was identified as a potential ceRNA sponge that may influence NK cell activity in HIRI. Our results underlined that the lncRNA-miRNA-mRNA ceRNA network can positively or negatively regulate immune-related functions and infiltrating immune cells mediated HIRI, which could provide further insight into novel molecular therapeutic targets.

## Linked entities

- **Genes:** PARD6G-AS1 (PARD6G antisense RNA 1) [NCBI Gene 100130522], PLAU (plasminogen activator, urokinase) [NCBI Gene 5328], CCR5 (C-C motif chemokine receptor 5) [NCBI Gene 1234], FGF5 (fibroblast growth factor 5) [NCBI Gene 2250], IL24 (interleukin 24) [NCBI Gene 11009]

## Full-text entities

- **Genes:** PARD6G-AS1 (PARD6G antisense RNA 1) [NCBI Gene 100130522], FGF5 (fibroblast growth factor 5) [NCBI Gene 2250] {aka HBGF-5, Smag-82, TCMGLY}, IL24 (interleukin 24) [NCBI Gene 11009] {aka C49A, FISP, IL10B, MDA7, MOB5, ST16}, CCR5 (C-C motif chemokine receptor 5) [NCBI Gene 1234] {aka CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5}, PLAU (plasminogen activator, urokinase) [NCBI Gene 5328] {aka ATF, BDPLT5, QPD, UPA, URK, u-PA}
- **Diseases:** HIRI (MESH:D015427)
- **Chemicals:** calcium (MESH:D002118)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12289005/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12289005/full.md

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Source: https://tomesphere.com/paper/PMC12289005