2. Academic Validation
  3. Hsa_circ_0008085 acts as a miR-146a-5p sponge to suppress influenza a virus replication via modulating of TRAF6

Hsa_circ_0008085 acts as a miR-146a-5p sponge to suppress influenza a virus replication via modulating of TRAF6

  • Int Immunopharmacol. 2025 Jun 5:157:114743. doi: 10.1016/j.intimp.2025.114743.
Hongjian Yan 1,  Xiangyu Zhu 2,  Daining Zhang 3,  Kaichun Zhang 3,  Ning Shi 4,  Xidong Liu 5
Affiliations

Affiliations

  • 1 College of Biological and Pharmaceutical Engineering, Jilin Agricultural Science and Technology University, Jilin 132101, China; State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • 2 College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China.
  • 3 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • 4 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address: shining17@jlu.edu.cn.
  • 5 College of Biological and Pharmaceutical Engineering, Jilin Agricultural Science and Technology University, Jilin 132101, China. Electronic address: liuxidong@jlnku.edu.cn.
PMID: 40306111 DOI: 10.1016/j.intimp.2025.114743
Abstract

Influenza A virus (IAV) has attracted considerable attention in recent years due to its increase in incidence and threat to human health. Circular RNA (circRNA) is a non-coding RNA with a closed structural pattern, which often acts as a Sponge for MicroRNAs (miRNAs) in the cell. A growing body of evidence supports several crucial roles for circRNAs in viral Infection, including regulation of viral replication, evasion of the host immune response and disease pathogenesis. However, due to the wide variety of circRNAs, their potential functions in IAV Infection remain to be elucidated. In this study, we determined that the expression of hsa_circ_0008085 was induced by IAV Infection. In addition, the JAK/STAT signaling pathway was associated with the induction of hsa_circ_0008085 in the context of IAV Infection, as evidenced by the application of ruxolitinib, a compound that inhibits the activation of the JAK/STAT pathway. In A549 cells, enhanced expression of hsa_circ_0008085 was found to repress viral gene expression and diminish the production of infectious progeny. In contrast, when hsa_circ_0008085 was knocked down, a significant boost in IAV replication was observed. Following a pull-down of RNA utilizing biotin and a luciferase reporter assay, we established that hsa_circ_0008085 binds with miR-146a-5p, functioning as an endogenous Sponge that suppresses the activity of miR-146a-5p. This interaction leads to an upregulation of TRAF6 expression, which in turn inhibits the replication of IAV. Conclusively, these data demonstrate that hsa_circ_0008085 inhibits viral replication via the miR-146a-5p/TRAF6 axis, highlighting the promising role of circRNAs in Antiviral therapies.

Keywords

Influenza a virus; Replication; circRNA; hsa_circ_0008085; miR-146a-5p.

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