Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 54 min ago
Peer-reviewedCC BY 4.0Advanced Science

EBV‐Driven ODC1 Upregulation Enhances Polyamine Anabolism to Promote Viral Replication and Cisplatin Resistance in Nasopharyngeal Carcinoma

  • Yueshuo Li1,2,3
  • Xudong Hu2,3
  • Chenxing Yang2,3
  • Na Liu2,3
  • Lin Wang2,3
  • Xi Cai2,3
  • Min Tang2,3,4
  • Ya Cao2,3,4
  • Li Shang1,2,3
  • Feng Shi1,2,3
4 affiliations
  1. 1Department of Pathology Xiangya Hospital Central South University Changsha China
  2. 2National Clinical Research Center for Geriatric Diseases Xiangya Hospital Central South University Changsha China
  3. 3Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education Cancer Research Institute Xiangya School of Basic Medical Sciences Central South University Changsha China
  4. 4Molecular Imaging Research Center of Central South University Changsha Hunan China
Read full textDOICite

Abstract

Epstein‐Barr virus (EBV) is a key oncogenic driver of nasopharyngeal carcinoma (NPC) and is closely associated with cisplatin resistance, but its roles in metabolic reprogramming and chemoresistance remain unclear. This study aimed to investigate the role of EBV in polyamine metabolic reprogramming and its underlying mechanism in mediating cisplatin resistance in NPC. Metabolomic and Metabolic Flux Analysis confirmed that EBV significantly enhances polyamine anabolism in NPC cells, with ODC1, the rate‐limiting enzyme of polyamine biosynthesis, transcriptionally upregulated by EBV‐BZLF1 via direct binding to its promoter. Functional experiments revealed that the ODC1‐spermidine axis promotes EBV replication and cell proliferation via eIF5A hypusination by upregulating EBV‐EAD and host TRAF1, respectively, and induces B‐to‐Z DNA transition to attenuate cGAS‐STING‐mediated innate immune responses. Clinically, high ODC1 expression was an independent prognostic marker for poor survival in NPC patients. In vitro and in vivo, ODC1 knockdown or pharmacological inhibition with DFMO effectively restored cisplatin sensitivity in EBV‐positive NPC cells, likely by reducing Z‐DNA formation and potentiating cisplatin‐induced innate immune responses. Collectively, our findings identify a novel EBV‐ODC1‐polyamine regulatory axis that promotes viral replication and confers a survival advantage to cancer cells, highlighting ODC1 as a promising therapeutic target to improve cisplatin efficacy in EBV‐positive NPC.

Related

  1. Unveiling crosstalk regulations within the polyamine pathway and between polyamine and purine pathways in Aedes aegypti females
    Jun Isoe, Thomas D. Horvath, Vlad Orlovsky +3
    Insect biochemistry and molecular biologyPeer-reviewedCC BY-NC 4.0Full textMolecular biology & gene regulationPMC
  2. Metabolic rewiring at the obesity-estrogen-polyamine axis in endometrial cancer: emerging mechanisms and translational opportunities.
    Daniel Simancas-Racines, Dolores Jima Gavilanes, Andri Matos +2
    Frontiers in cell and developmental biologyPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMC
  3. Direct detection of electrogenic polyamine transport
    S. R. Cleary, C. Moreno, S. Srivastava +3
    bioRxivPreprintCC BYFull textBiophysicsbioRxiv
  4. Dual role of RBM3 in PEDV infection: stabilization of viral RNA and upregulation of the entry factor HSPA5
    L. Siyu, Z. Yan, L. Jinze +11
    bioRxivPreprintAll rights reservedFull textMolecular biology & gene regulationbioRxiv
  5. Condensin upregulation induces intestinal stem cell senescence, driving cell death and increased intestinal permeability
    Afshin Khan, Greeshma Ray, Ryan Musich +14
    iSciencePeer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationCell biologyCell PressCrossrefEurope PMC

Cite

BibTeXRIS
BibTeX
@article{li2026ebvdriven,
  title = {{EBV‐Driven ODC1 Upregulation Enhances Polyamine Anabolism to Promote Viral Replication and Cisplatin Resistance in Nasopharyngeal Carcinoma}},
  author = {Yueshuo Li and Xudong Hu and Chenxing Yang and Na Liu and Lin Wang and Xi Cai and Min Tang and Ya Cao and Li Shang and Feng Shi},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77204},
  url = {https://doi.org/10.1002/advs.77204},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - EBV‐Driven ODC1 Upregulation Enhances Polyamine Anabolism to Promote Viral Replication and Cisplatin Resistance in Nasopharyngeal Carcinoma
AU  - Yueshuo Li
AU  - Xudong Hu
AU  - Chenxing Yang
AU  - Na Liu
AU  - Lin Wang
AU  - Xi Cai
AU  - Min Tang
AU  - Ya Cao
AU  - Li Shang
AU  - Feng Shi
PY  - 2026
DA  - 2026/08/15
JO  - Advanced Science
DO  - 10.1002/advs.77204
UR  - https://doi.org/10.1002/advs.77204
AB  - Epstein‐Barr virus (EBV) is a key oncogenic driver of nasopharyngeal carcinoma (NPC) and is closely associated with cisplatin resistance, but its roles in metabolic reprogramming and chemoresistance remain unclear. This study aimed to investigate the role of EBV in polyamine metabolic reprogramming and its underlying mechanism in mediating cisplatin resistance in NPC. Metabolomic and Metabolic Flux Analysis confirmed that EBV significantly enhances polyamine anabolism in NPC cells, with ODC1, the rate‐limiting enzyme of polyamine biosynthesis, transcriptionally upregulated by EBV‐BZLF1 via direct binding to its promoter. Functional experiments revealed that the ODC1‐spermidine axis promotes EBV replication and cell proliferation via eIF5A hypusination by upregulating EBV‐EAD and host TRAF1, respectively, and induces B‐to‐Z DNA transition to attenuate cGAS‐STING‐mediated innate immune responses. Clinically, high ODC1 expression was an independent prognostic marker for poor survival in NPC patients. In vitro and in vivo, ODC1 knockdown or pharmacological inhibition with DFMO effectively restored cisplatin sensitivity in EBV‐positive NPC cells, likely by reducing Z‐DNA formation and potentiating cisplatin‐induced innate immune responses. Collectively, our findings identify a novel EBV‐ODC1‐polyamine regulatory axis that promotes viral replication and confers a survival advantage to cancer cells, highlighting ODC1 as a promising therapeutic target to improve cisplatin efficacy in EBV‐positive NPC.
SN  - 2198-3844
ER  -