Exploring the role of miRNAs in Hepatocellular Carcinoma: Insights into signaling pathways and their regulatory mechanisms.

Objective: This prospective case-control study aimed to assess the predictive value of the expression levels of Hsa-miR-200-3p, Hsa-miR-155-5p, Hsa-miR-20a-5p, Hsa-miR-221-3p, Hsa-miR-34a-5p, Hsa-let-7b-5p, and Hsa-miR-125b-5p microRNAs (miRNAs) in the diagnosis, prognosis, and treatment response of hepatocellular carcinoma (HCC) patients. The study includes 20 healthy controls and 25 HCC patients. Methods: The study was designed as a prospective case-control study and was conducted between 2023 to 2024 at Ataturk University, in collaboration with the Departments of Organ Transplantation, Medical Biology and Medical Pathology. miRNA expression levels were examined in HCC tissue samples. RNA was extracted from paraffin-embedded tissues, and miRNA expression levels were measured using reverse transcription-quantitative PCR. The relationships between clinical factors and miRNA expression levels were assessed. Results: Significant differences in expression levels were found between HCC tissues and healthy control tissues for Hsa-miR-20a-5p, Hsa-miR-125b-5p, and Hsa-let-7b-5p. A significant correlation was observed between Hsa-miR-34a-5p and γ-glutamyl transferase levels (P<0.05), as well as between Hsa-miR-20a-5p and albumin levels (P<0.05). Significant differences in expression levels were found between patients with and without HBV infection for let-7b-5p (P=0.007) and miR-200-3p (P=0.013). Conclusion: This study demonstrates that miRNAs, particularly Hsa-miR-20a-5p and Hsa-miR-34a-5p, may regulate the Wnt/β-catenin pathway and influence the progression of HCC. Disease progression was assessed by comparing miRNA expression levels with clinical markers (such as γ-glutamyl transferase and albumin). High expression of Hsa-miR-20a-5p affects the Wnt/β-catenin pathway and plays a significant role in disease processes. Additionally, the correlation between Hsa-miR-34a-5p and γ-glutamyl transferase indicates disease progression. However, further advanced studies are required to better understand how the Wnt/β-catenin pathway is regulated by miRNAs and the impact of this regulation on the disease.