MiR-4725-3p acts as an oncogene and prognostic biomarker in hepatocellular carcinoma

  • World J Surg Oncol. 2026 May 23;24(1):296. doi: 10.1186/s12957-026-04384-6.
Xiumin Zhao  #  1 ,  Zhenhong Chang  #  2 ,  Jinmin Su  3 ,  Jiaoling Gu  3 ,  Zhizhong Lu  4 ,  Peng Dai  5
Affiliations
  • 1. Intervention Department, Chifeng Cancer Hospital, Chifeng, Inner Mongolia Autonomous Region, 024000, China.
  • 2. Department of Traditional Chinese Medicine Gastroenterology, Shijiazhuang Gaocheng People's Hospital, Shijiazhuang, 052106, China.
  • 3. Department of Clinical Laboratory, The 966th Hospital of The PLA Joint Logistic Support Forse, Dandong, Liaoning, 118000, China.
  • 4. Department of Clinical Laboratory, Jiaozuo People's Hospital, Jiaozuo, 454002, China.
  • 5. Department of General Medicine, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, No. 3, Employee New Village, Xinghualing District, Taiyuan, 030013, China. [email protected].
  • # Contributed equally.
PMID: 42177572 DOI: 10.1186/s12957-026-04384-6
Abstract

Background: Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm with high incidence and dismal prognostic outcomes.

Purpose: This study sought to validate the prognostic significance of miR-4725-3p in HCC and the possible molecular mechanism.

Methods: A total of 117 HCC patients were stratified into two groups according to the median expression level of miR-4725-3p. Following a 5-year follow-up with death as the end event, a Kaplan-Meier curve was drawn. The potential risk factors for poor prognosis were evaluated using COX regression analysis. Cell Counting Kit-8 (CCK-8) and Transwell assay were employed to assess the role of miR-4725-3p silencing on Huh-7 and Hep3B cells viability and migration. Downstream target genes of miR-4725-3p were predicted, and a dual-luciferase assay was conducted to verify the interaction.

Results: MiR-4725-3p was significantly upregulated in HCC tissue and cell line. Survival analysis showed that high miR-4725-3p expression was associated with poor prognosis in HCC patients (log-rank P = 0.006). At the cellular level, silencing miR-4725-3p significantly suppressed the viability and migration of Huh-7 and Hep3B cells. Mechanistically, activating transcription factor 5 (ATF5) was identified as a direct target of miR-4725-3p. ATF5 was downregulated in HCC tissue and cells.

Conclusion: The results of this study revealed that miR-4725-3p serves as a promising prognostic biomarker for HCC, and its oncogenic role in promoting HCC cell viability and migration may be mediated, at least in part, via the negative regulation of ATF5.

Keywords
ATF5; Hepatocellular carcinoma; MiR-4725-3p; Prognosis.
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