J Appl Biomed 24:10-26, 2026 | DOI: 10.32725/jab.2026.002

miR-500a-3p negatively regulates SOCS2 and participates in the proliferation, glycolysis, and apoptosis of HCC cells via the JAK2/STAT5 pathway

Shan Li ORCID...¹, Wei Luo ORCID...², Wei Liu ORCID...^{3, *}

¹ Affiliated Hospital of Hubei University of Science and Technology, Xiantao First People's Hospital, Department of Endocrinology, Xiantao City 433000, Hubei Province, China

² Jianli People's Hospital Affiliated to China Three Gorges University, Department of Oncology, Rongcheng Town, Jianli City 433300, Hubei Province, China

³ Affiliated Hospital of Hubei University of Science and Technology, Xiantao First People's Hospital, Department of Gastrointestinal Surgery, Xiantao City 433000, Hubei Province, China

Background: HCC is a prevalent malignant tumor globally with high mortality. MiR-500a-3p plays critical roles in tumorigenesis and tumor progression.

Methods: To evaluate miR-500a-3p's role in HCC, we first analyzed its expression and prognostic value via qRT-PCR and TCGA (Kaplan-Meier analysis). We then performed extensive in vitro functional studies after cell transfection (mimics, anti-miR, SOCS2 OE), measuring proliferation, migration, invasion, glycolytic parameters (glucose consumption, lactate, ECAR, ATP), and apoptosis. A target relationship with SOCS2 was predicted bioinformatically and confirmed by dual-luciferase assay. Using the JAK2/STAT5 signaling pathway inhibitor Fedratinib, the activator Erythropoietin, and transfection with si-STAT5 and oe-STAT5, the molecular mechanism of miR-500a-3p in HCC was investigated. In vivo experiments established tumor-bearing mouse models to evaluate the effect of miR-500a-3p on tumor growth.

Results: miR-500a-3p was significantly upregulated in HCC tissues and cells, and was associated with poor patient prognosis. The overexpression of miR-500a-3p promotes the malignant progression of HCC cells. Mechanistically, miR-500a-3p directly targeted and negatively regulated SOCS2 expression. SOCS2 expression was suppressed in HCC, with its expression abrogating miR-500a-3p-mediated oncogenicity. miR-500a-3p activated the JAK2/STAT5 pathway by inhibiting SOCS2, thereby regulating the malignant biological behaviors of HCC cells. Both SOCS2 overexpression and JAK2 inhibitor treatment could reverse the activation of the JAK2/STAT5 axis and downstream effects induced by miR-500a-3p. MiR-500a-3p promoted tumor growth in tumor-bearing mice, accompanied by SOCS2 downregulation and JAK2/STAT5 pathway activation.

Conclusion: This study reveals that miR-500a-3p promotes proliferation and glycolysis while inhibiting apoptosis of HCC cells by negatively regulating SOCS2 and activating the JAK2/STAT5 pathway.

Keywords: Apoptosis; Glycolysis; Hepatocellular carcinoma; miR-500a-3p; Proliferation; SOCS2

Conflicts of interest:

The authors confirm that no generative artificial intelligence tools were used in the preparation of this manuscript and have no conflict of interest to declare.

Received: September 19, 2025; Revised: February 27, 2026; Accepted: March 6, 2026; Prepublished online: March 9, 2026; Published: March 27, 2026  Show citation