# Circular RNAs in sepsis-induced acute lung injury: emerging mechanisms and therapeutic potential

**Authors:** Qinghai Liu, Yiyan Wang, Haitang Liao, Dongsheng Ren, Wenhui Guo, Jianzhong Xu, Chenyang Duan, Zhenchun Luo, Wen Jiang

PMC · DOI: 10.3389/fimmu.2026.1718164 · Frontiers in Immunology · 2026-02-18

## TL;DR

This review explores how circular RNAs may influence sepsis-related lung injury and could serve as potential biomarkers or treatments.

## Contribution

The paper systematically summarizes the emerging role of circRNAs in sepsis-induced acute lung injury and highlights their therapeutic potential.

## Key findings

- CircRNAs regulate inflammation, immune responses, and lung barrier integrity in sepsis.
- CircRNAs show promise as diagnostic biomarkers and therapeutic targets for sepsis-induced lung injury.
- Challenges remain in detecting circRNAs and validating their clinical utility in sepsis.

## Abstract

Sepsis-induced acute lung injury (ALI) remains a leading cause of mortality in critically ill patients and is characterized by dysregulated inflammation, immune imbalance, and alveolar–capillary barrier dysfunction. Emerging evidence suggests that circular RNAs (circRNAs), a class of stable and highly conserved non-coding RNAs, play important regulatory roles in inflammatory diseases; however, their contributions to sepsis-associated lung injury have not yet been systematically summarized. In this review, we provide a comprehensive overview of circRNA biogenesis, classification, and regulatory properties, with a particular focus on their context-dependent functions in the septic lung. We discuss how circRNAs participate in the coordination of cell fate decisions, immune responses, and barrier integrity during sepsis, and highlight their potential as diagnostic biomarkers and therapeutic targets. Importantly, we also address current technical and translational challenges, including detection specificity, disease heterogeneity, and limited clinical validation. By integrating mechanistic insights with translational perspectives, this review aims to clarify the emerging role of circRNAs in sepsis-induced ALI and to outline key directions for future research.

## Linked entities

- **Diseases:** acute lung injury (MONDO:0006502)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, ROCK1 (Rho associated coiled-coil containing protein kinase 1) [NCBI Gene 6093] {aka P160ROCK, ROCK-I}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, SOX6 (SRY-box transcription factor 6) [NCBI Gene 55553] {aka HSSOX6, SOXD, TOLCAS}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, ROCK2 (Rho associated coiled-coil containing protein kinase 2) [NCBI Gene 9475] {aka ROCK-II}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, MIR214 (microRNA 214) [NCBI Gene 406996] {aka MIRN214, miRNA214, mir-214}, VMA21 (vacuolar ATPase assembly factor VMA21) [NCBI Gene 203547] {aka MEAX, XMEA}, NOX4 (NADPH oxidase 4) [NCBI Gene 50507] {aka KOX, KOX-1, RENOX}, MIR497 (microRNA 497) [NCBI Gene 574456] {aka MIRN497, hsa-mir-497, mir-497}, SERP1 (stress associated endoplasmic reticulum protein 1) [NCBI Gene 27230] {aka RAMP4}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, EZH1 (enhancer of zeste 1 polycomb repressive complex 2 subunit) [NCBI Gene 2145] {aka KMT6B}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CD2AP (CD2 associated protein) [NCBI Gene 23607] {aka CMS}, ACSL4 (acyl-CoA synthetase long chain family member 4) [NCBI Gene 2182] {aka ACS4, FACL4, LACS4, MRX63, MRX68, XLID63}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, PRKCI (protein kinase C iota) [NCBI Gene 5584] {aka DXS1179E, PKCI, nPKC-iota}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, RBM33 (RNA binding motif protein 33) [NCBI Gene 155435] {aka PRR8}, VAPA (VAMP associated protein A) [NCBI Gene 9218] {aka VAMP-A, VAP-33, VAP-A, VAP33, hVAP-33}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, MIR375 (microRNA 375) [NCBI Gene 494324] {aka MIRN375, hsa-mir-375, miRNA375, mir-375}, ELAVL1 (ELAV like RNA binding protein 1) [NCBI Gene 1994] {aka ELAV1, HUR, Hua, MelG}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, PTBP1 (polypyrimidine tract binding protein 1) [NCBI Gene 5725] {aka HNRNP-I, HNRNPI, HNRPI, PTB, PTB-1, PTB-T}
- **Diseases:** critically ill (MESH:D016638), injury (MESH:D014947), HL (MESH:C538324), inflammation (MESH:D007249), lung injury (MESH:D055370), pulmonary edema (MESH:D011654), ALI (MESH:D055371), lung barrier dysfunction (MESH:D008171), cancer (MESH:D009369), inflammatory syndromes (MESH:D018746), infection (MESH:D007239), cardiovascular disease (MESH:D002318), lung inflammation (MESH:D011014), paralysis (MESH:D010243), depression (MESH:D003866), cytokine storm (MESH:D000080424), Sepsis (MESH:D018805), tissue damage (MESH:D017695), ARDS (MESH:D012128), septic (MESH:D001170), necrosis (MESH:D009336), neurological disorders (MESH:D009461), immune dysregulation (OMIM:614878)
- **Chemicals:** N6-methyladenosine (MESH:C010223), LPS (MESH:D008070), lipid (MESH:D008055), iron (MESH:D007501), m6A (MESH:C005955)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

121 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956634/full.md

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Source: https://tomesphere.com/paper/PMC12956634