The Role of Circular RNAs in Hepatocellular Carcinoma: Mechanisms, Implications, and Therapeutic Potential
DOI:
https://doi.org/10.60087/jklst.vol4.n4.009Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies and a predominant cause of cancer-related death worldwide, featuring high metastasis potential and resistance to chemotherapeutic agents. Both early diagnosis and good treatment options remain major challenges of HCC management. Recent studies have shown that exosomal circRNAs (circular RNAs) can serve as promising diagnostic and therapeutic markers for cancers, given their stability in biological fluids and the involvement of many oncogenic pathways through which they regulate cancer progression. Methods: This review focuses specifically on exosomal circRNAs, examining their functions during tumor progression, metastasis, and chemoresistance in HCC. We also describe the ways circRNAs are involved in miRNA-mediator interactions and epigenetic regulation of HCC. We performed a systematic review of the literature, including articles published up to 2015-2025, in the databases of PubMed, Google Scholar, and Web of Science. We selected relevant studies focusing on circRNAs and their involvement in HCC along with miRNA interactions. Outcomes: The extensive involvement of exosomal circRNAs in modulating miRNA signaling pathways leads to modulation of processes such as angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis in HCC. They further also promote chemoresistance by modulating the processes of drug resistance and immune evasion. Moreover, circRNA87th53-derived CE-Ang1 is a promising therapy for HCC. Conclusion: Exosomal circRNAs present potential as promising biomarkers and therapeutic targets for HCC. More studies should be performed to investigate their clinical implications and to resolve problems with circRNA identification and functional delivery.
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