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Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review)

  • Authors:
    • Weihua Xu
    • Zhichao Ma
    • Wei Gong
    • Shengmiao Fu
    • Xinping Chen
  • View Affiliations / Copyright

    Affiliations: Department of Medical Laboratory, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan 570312, P.R. China, School of Life Sciences, Hainan University, Haikou, Hainan 570228, P.R. China, Hainan Lvtou Medical Laboratory Center, Haikou, Hainan 570206, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 82
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    Published online on: August 18, 2025
       https://doi.org/10.3892/ijo.2025.5788
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Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy closely associated with Epstein‑Barr virus (EBV) infection. Although patients with early‑stage NPC can achieve a high cure rate through radiotherapy, recurrence and distant metastasis remain the primary causes of treatment failure in patients with advanced‑stage NPC. Circular RNA (circRNA) is a class of covalently closed non‑coding RNAs involved in multiple aspects of tumor biology. Recent evidence has shown that certain circRNAs can encode functional peptides, which participate in the regulation of tumor‑related signaling pathways. In NPC, circRNAs have been implicated in the modulation of signaling pathways, including NF‑κB and JAK/STAT, both of which are activated in the EBV‑infected microenvironment. Furthermore, frequently mutated genes in NPC, such as TNF receptor‑associated factor 3 and cylindromatosis lysine 63 deubiquitinase, are known regulators of the NF‑κB pathway, suggesting a potential link between genetic alterations and circRNA‑related mechanisms. This article systematically reviews the biological mechanisms of circRNA‑encoded peptides, summarizes the expression and function of circRNA in NPC and focuses on discussing the potential roles of circRNA‑encoded peptides in tumor microenvironment regulation, immune escape and clinical application prospects. By integrating existing research results, this article aims to provide a new perspective and theoretical basis for the in‑depth exploration of circRNA‑encoded peptides in the field of NPC.
View Figures

Figure 1

Translation mechanisms of circRNAs.
There are three translation modes for circRNAs, including
IRES-initiated translation, which starts protein synthesis via the
IRES site; MIRES-initiated translation, which is assisted by the
YTHDF protein; and infinite ORF rolling translation, which
generates proteins through a continuous translation cycle. EcRNA,
elciRNA, and ciRNA are different types of circRNAs with distinct
origins and functions. IRES, internal ribosome entry site; circRNA,
circular RNA; MIRES, m6A-initiated internal ribosome entry site;
m6A, N6-methyladenosine; ORF, open reading frame; YTHDF, YTH
N6-methyladenosine RNA-binding protein family; EcRNA, exonic
circRNA; elciRNA, exon-intron circRNA; ciRNA, circular intronic
RNA.

Figure 2

EBV infection activates NF-κB and
JAK/STAT pathways in NPC. CircRNAs may encode peptides that
modulate these oncogenic signals. Loss of TRAF3 and CYLD enhances
NF-κB activation. Red dashed lines and question marks indicate
hypothetical links. NPC, nasopharyngeal carcinoma; circRNA,
circular RNA; EBV, Epstein-Barr virus; LMP1, latent membrane
protein 1; TRAF3, TNF receptor-associated factor 3; CYLD,
cylindromatosis; NF-κB, nuclear factor κ-light-chain-enhancer of
activated B cells; JAK2, Janus kinase 2; STAT3, signal transducer
and activator of transcription 3.
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Copy and paste a formatted citation
Spandidos Publications style
Xu W, Ma Z, Gong W, Fu S and Chen X: Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review). Int J Oncol 67: 82, 2025.
APA
Xu, W., Ma, Z., Gong, W., Fu, S., & Chen, X. (2025). Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review). International Journal of Oncology, 67, 82. https://doi.org/10.3892/ijo.2025.5788
MLA
Xu, W., Ma, Z., Gong, W., Fu, S., Chen, X."Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review)". International Journal of Oncology 67.4 (2025): 82.
Chicago
Xu, W., Ma, Z., Gong, W., Fu, S., Chen, X."Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review)". International Journal of Oncology 67, no. 4 (2025): 82. https://doi.org/10.3892/ijo.2025.5788
Copy and paste a formatted citation
x
Spandidos Publications style
Xu W, Ma Z, Gong W, Fu S and Chen X: Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review). Int J Oncol 67: 82, 2025.
APA
Xu, W., Ma, Z., Gong, W., Fu, S., & Chen, X. (2025). Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review). International Journal of Oncology, 67, 82. https://doi.org/10.3892/ijo.2025.5788
MLA
Xu, W., Ma, Z., Gong, W., Fu, S., Chen, X."Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review)". International Journal of Oncology 67.4 (2025): 82.
Chicago
Xu, W., Ma, Z., Gong, W., Fu, S., Chen, X."Functional mechanisms of circular RNA‑encoded peptides and future research strategies and directions in nasopharyngeal carcinoma (Review)". International Journal of Oncology 67, no. 4 (2025): 82. https://doi.org/10.3892/ijo.2025.5788
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