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Dysregulation of MicroRNAs in Hepatocellular Carcinoma: Targeting Oncogenic Signaling Pathways for Innovative
Yusra Zarlashat1, Judit Halász2, Edit Dósa3
1Department of Biochemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Abstract:
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the third leading cause of cancer-related death. Hyperactivation of oncogenes and suppression of tumor suppressor genes/proteins drive HCC initiation and progression. MicroRNAs (miRNAs) critically modulate HCC biology by regulating proliferation, apoptosis, and metastasis. Acting either as tumor suppressors or oncomiRs, they shape core signaling pathways, including PI3K/Akt/mTOR, Hippo-YAP/TAZ, Wnt/β-catenin, RAS/MAPK, and p53. Their dysregulation in tissues and body fluids renders them promising diagnostic biomarkers and therapeutic targets. Preclinical studies demonstrate that miRNA-based strategies-either restoring tumor-suppressive miRNAs (e.g., miR-34a, miR-125a-5p) or inhibiting oncogenic miRNAs (e.g., miR-660-5p)-can suppress HCC progression and reduce treatment resistance. Combination approaches, such as pairing miR-122 mimics with miR-221 inhibitors or delivering miR-326 via nanoparticles, further enhance efficacy by simultaneously targeting multiple oncogenic pathways. This review summarizes recent advances in miRNA-mediated regulation of HCC signaling and highlights their clinical potential, including ongoing trials of miRNA-based diagnostics and therapeutics for early detection, prognostication, and personalized treatment.
Insights
MicroRNAs (miRNAs) regulate hepatocellular carcinoma (HCC) development by controlling key signaling pathways. miRNA-based therapies show promise for diagnosing and treating HCC, offering new personalized treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) is a major global cancer with high mortality.
- Oncogene activation and tumor suppressor gene loss drive HCC.
- MicroRNAs (miRNAs) are crucial regulators of HCC cell proliferation, apoptosis, and metastasis.
Purpose of the Study:
- To review miRNA's role in regulating HCC signaling pathways.
- To highlight the diagnostic and therapeutic potential of miRNAs in HCC.
- To summarize recent advances in miRNA-based HCC treatment strategies.
Main Methods:
- Literature review of preclinical and clinical studies on miRNAs in HCC.
- Analysis of miRNA involvement in key signaling pathways (PI3K/Akt/mTOR, Hippo-YAP/TAZ, Wnt/β-catenin, RAS/MAPK, p53).
- Evaluation of miRNA-based diagnostic biomarkers and therapeutic approaches.
Main Results:
- miRNAs act as tumor suppressors or oncomiRs, influencing HCC progression.
- Dysregulated miRNAs in tissues and body fluids are potential biomarkers.
- miRNA-based strategies (restoring tumor suppressors, inhibiting oncomiRs) show efficacy in preclinical HCC models.
- Combination therapies and targeted delivery enhance miRNA therapeutic effects.
Conclusions:
- miRNAs are critical regulators of HCC biology and signaling pathways.
- miRNAs represent promising biomarkers for HCC early detection and prognostication.
- miRNA-based therapeutics offer potential for personalized HCC treatment and overcoming resistance.
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