Tumor Suppressive Effect of miRNA-205-3p on Hepatocellular Carcinoma via Regulating ZDBF2

Indian Journal of Pharmaceutical Education and Research

  • Xin Lu1Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, CHINA.
  • Wenting Mi2Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, CHINA.
  • Jianming Zheng1Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, CHINA.
  • Meishi Tang1Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, CHINA.
  • Haoxiang Ou1Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, CHINA.
  • Yubin Liu1Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, CHINA.

Volume 60 Issue 4 Pages 1801-1809

DOI: 10.5530/ijper.20264811

Abstract

Objectives: The present study aimed to clarify the functional involvement of microRNA-205-3p (miRNA-205-3p) in Hepatocellular Carcinoma (HCC) progression and to determine its potential clinical relevance in predicting disease behaviour and patient prognosis. Materials and Methods: Quantitative real-time PCR analysis was conducted to determine miRNA-205-3p expression in hepatocellular carcinoma specimens and matched adjacent liver tissues. Correlations between miRNA-205-3p levels and clinicopathological variables were subsequently analyzed. Functional experiments were carried out in Hep3B and Huh7 cells following ectopic miRNA-205-3p upregulation to evaluate its influence on proliferative capacity, clonogenicity, migratory behavior, and invasive potential. Cell growth was monitored using CCK-8 and colony formation assays, whereas transwell assays were employed to assess migration and invasion. In addition, the regulatory relationship between miRNA-205-3p and ZDBF2 was confirmed through luciferase reporter experiments. Rescue experiments were subsequently conducted to determine whether ZDBF2 mediated the phenotypic effects induced by miRNA-205-3p. Results: A substantial downregulation of miRNA-205-3p was identified in hepatocellular carcinoma tissues relative to matched non-cancerous liver specimens, with metastatic tumors showing the lowest expression levels. Decreased miRNA-205-3p expression was associated with lymph node metastasis, distant metastasis, shorter progression-free survival, and poorer overall survival. Functional restoration of miRNA-205-3p suppressed proliferation, clonogenic growth, migration, and invasion in Hep3B and Huh7 cells. Consistently, miRNA-205-3p overexpression restrained tumor growth in nude mouse xenograft models. Mechanistically, ZDBF2 was identified as a direct downstream target of miRNA-205-3p and showed an inverse expression relationship with miRNA-205-3p. Recovery of ZDBF2 expression counteracted, to some extent, the suppressive influence of miRNA-205-3p on aggressive cellular behaviors. Conclusion: MiRNA-205-3p was downregulated in HCC and appeared to suppress malignant progression by directly targeting ZDBF2. These findings suggest that the miRNA-205-3p/ZDBF2 axis may serve as a promising molecular target for HCC prognosis assessment and therapeutic intervention.

Keywords

  • Hepatocellular carcinoma
  • Invasion
  • Metastasis
  • Migration
  • miRNA-205-3p
  • Tumor suppression
  • ZDBF2
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