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Review
. 2025 May;27(5):e70019.
doi: 10.1002/jgm.70019.

Natural Products as Modulators of miRNA in Hepatocellular Carcinoma: A Therapeutic Perspective

Affiliations
Review

Natural Products as Modulators of miRNA in Hepatocellular Carcinoma: A Therapeutic Perspective

Shahzada Khalid Sohail. J Gene Med. 2025 May.

Abstract

Hepatocellular carcinoma (HCC) continues to pose a substantial worldwide health concern, marked by elevated mortality rates and restricted therapeutic alternatives. Recent studies have highlighted the potential of natural compounds as therapeutic agents in cancer management. This review focuses on the diagnostic and prognostic potential of microRNAs (miRNAs) as biomarkers in HCC, alongside the therapeutic promise of natural products. We explore the intricate role of miRNAs in the pathogenesis of HCC, detailing their regulatory functions in cellular processes such as proliferation, apoptosis, and metastasis. Additionally, we discuss the emerging evidence supporting the use of natural compounds, including phytochemicals, in modulating miRNA expression and their potential synergistic effects with conventional therapies. Key miRNAs discussed include miR-21, an oncogenic factor that promotes tumor growth by targeting the tumor suppressor phosphatase and tensin homolog (PTEN); miR-34a, which enhances apoptosis and may improve treatment efficacy when combined with c-MET inhibitors; miR-203, whose downregulation correlates with poor outcomes and may serve as a prognostic marker; miR-16, which acts as a tumor suppressor and has diagnostic potential when measured alongside traditional markers like alpha-fetoprotein (AFP); and miR-483-3p, associated with resistance to apoptosis and tumor progression. By integrating insights from recent studies, this review aims to highlight the dual role of miRNAs as both biomarkers and therapeutic targets, paving the way for enhanced diagnostic strategies and novel treatment modalities in HCC management.

Keywords: diagnosis; hepatocellular carcinoma; natural products; oncogenic miRNAs; pathogenesis; tumor suppressor miRNAs.

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