Circular RNA in hepatocellular carcinoma : emerging therapeutic strategies

Jazbec, Gregor (author), Režen, Tadeja (author)

Circular RNAs, or circRNAs, are unique single-stranded RNA molecules that form covalently closed circles. They possess a wide range of cellular functions and can act as tumor suppressors or promoters, regulating various aspects of carcinogenesis. These functions include acting as microRNA sponges, nteracting with and binding to proteins and mRNA, regulating transcription and RNA splicing, translating into proteins, and serving as cargo in exosomes. Due to their diverse cellular roles and enhanced molecular stability, circRNAs are not only promising biomarkers but also emerging candidates for the development of RNA-based therapeutics. In this review, we explored the therapeutic potential of circular RNA by reviewing the current state of the art n the field of oncology, with a particular focus on hepatocellular carcinoma. Based on their endogenous functions, circular RNA can be designed, synthesized and delivered to produce various proteins, such as neoantigens and cytokines, or to sequester oncogenic microRNA in tumor cells. Although many therapeutic applications of circular RNA are still in the early stages of development, they have already shown promising results in both in vitro and in vivo animal models. In summary, circular RNAs are emerging as both therapeutics and biomarkers in iver cancer and broader oncology, with relevant clinical applicability, particularly n immunotherapy.

• Language: English
• Keywords: RNA-based therapeutics, circRNA, circRNA-based therapeutics, hepatocellular carcinoma, immunotherapy
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Submitted for review: 20.11.2025
• Article acceptance date: 25.11.2025
• Publication date: 09.12.2025
• Year: 2025
• Number of pages: 16 str.
• Numbering: Vol. 16, art. 1722576
• PID: 20.500.12556/RUL-177805
• UDC: 577.2
• ISSN on article: 1664-3224
• DOI: 10.3389/fimmu.2025.1722576
• COBISS.SI-ID: 263803139
• Publication date in RUL: 08.01.2026

Record is a part of a journal

• Title: Frontiers in immunology
• Shortened title: Front. immunol.
• Publisher: Frontiers Media
• ISSN: 1664-3224
• COBISS.SI-ID: 30774233

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: terapija na osnovi RNA, cirkularna RNA, terapija na osnovi cirkularne RNA, hepatocelularni karcinom, imunoterapija