# Long noncoding RNA ADEI/miR-93-3p/STAT3 axis promotes Epstein–Barr virus-positive diffuse large B-cell lymphoma progression and immune evasion through regulating the PD-1/PD-L1 checkpoint

**Authors:** Weili Zheng, Guilan Lai, Ziyuan Liao, Jianzhen Shen

PMC · DOI: 10.1038/s41419-026-08532-4 · 2026-03-03

## TL;DR

A new long noncoding RNA called lncADEI helps Epstein-Barr virus-positive lymphoma grow and avoid the immune system by boosting PD-L1.

## Contribution

The study identifies lncADEI as a novel lncRNA that promotes EBV+ DLBCL progression and immune evasion via the miR-93-3p/STAT3/PD-L1 axis.

## Key findings

- LncADEI is upregulated in EBV+ DLBCL and promotes cell proliferation and clonogenesis.
- LncADEI activates STAT3 via miR-93-3p, which increases PD-L1 expression and immune evasion.
- LncADEI is present in serum exosomes of EBV+ DLBCL patients and correlates with poor outcomes.

## Abstract

Epstein–Barr virus (EBV) is an important pathogenic factor of lymphoma; EBV+diffuse large B-cell lymphoma (DLBCL) has a worse prognosis with standard chemotherapy than EBV-DLBCL. Long noncoding (Lnc)-RNAs are key regulators of cancer pathways and biomarkers of disease. As natural protective carriers of noncoding RNAs, exosomes can stably transmit signals during tumor development. We explored the role of exosomal lncRNAs in the occurrence and development of EBV-related DLBCL. In this study, we identified a novel lncRNA lncADEI, which was upregulated in EBV + DLBCL and was positively correlated with DLBCL cell proliferation and clonogenesis. LncADEI positively regulated STAT3 via miR-93-3P, and STAT3 transcriptionally activated programmed death ligand-1 to promote immune evasion of DLBCL cells. LncADEI could be transferred by exosomes and promote the proliferation and immune evasion of DLBCL. LncADEI was highly expressed in serum exosomes from EBV + DLBCL patients and was associated with worse clinicopathological features. In conclusion, lncADEI participated in the progression and immune evasion of EBV + DLBCL and was differentially expressed in serumal exosomes. LncADEI may be a promising strategy for treating EBV-associated lymphoid malignancies.

## Linked entities

- **Genes:** adeI (multidrug efflux RND transporter periplasmic adaptor subunit AdeI) [NCBI Gene 9381125], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774], CD274 (CD274 molecule) [NCBI Gene 29126]
- **Diseases:** diffuse large B-cell lymphoma (MONDO:0018905)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, MIR933 (microRNA 933) [NCBI Gene 100126350] {aka MIRN933, hsa-mir-933, mir-933}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}
- **Diseases:** DLBCL (MESH:D016403), lymphoma (MESH:D008223), cancer (MESH:D009369), EBV-associated lymphoid malignancies (MESH:D020031)
- **Species:** human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13018472/full.md

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Source: https://tomesphere.com/paper/PMC13018472