Circular RNAs in hepatocellular carcinoma: a systematic qualitative review of regulatory mechanisms, therapeutic resistance, and clinical translation
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by high mortality, frequent recurrence, and limited long-term benefit from systemic therapy and radiotherapy. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs with high molecular stability and tissue-specific expression, have emerged as important regulators of HCC biology and treatment response.
METHODS: We searched PubMed from database inception to May 2, 2026 and manually screened the reference lists of eligible studies and relevant reviews for studies investigating circRNA-related molecular mechanisms, tumor progression, therapeutic resistance, radiotherapy response, or translational applications in HCC. A total of 694 records were identified in PubMed, 694 records were screened after duplicate removal, and 42 studies were included in the qualitative synthesis. Original studies involving human tissues, clinical cohorts, cell lines, or animal models were eligible. Title/abstract screening, full-text assessment, and data extraction were performed independently by two reviewers, with disagreements resolved by consensus or senior-author adjudication. Given substantial heterogeneity in study design, model systems, molecular endpoints, and reported outcomes, findings were synthesized qualitatively rather than by meta-analysis, and a structured qualitative evidence appraisal was used to weight mechanistic and translational conclusions.
RESULTS: The included evidence indicates that circRNAs…
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