microRNA-27a-3p influences hepatocellular carcinoma cell migration and invasion via the TET1/p53 pathway.

OBJECTIVE: This work aims to analyze the clinical significance of microRNA-27a-3p (miR-27a-3p) in hepatocellular carcinoma (HCC) and its impact on HCC cell behavior. METHODS: RT-qPCR was performed on 57 paired HCC tumor and adjacent normal tissues to assess miR-27a-3p levels and its correlation with prognosis and clinicopathological features. HCC cells were transfected with miR-27a-3p inhibitor/mimic, si-TET1, or corresponding controls. RT-qPCR/Western blot measured miR-27a-3p, TET1, and p53 levels. CCK-8/Transwell/flow cytometry assay evaluated cell activities. Dual-luciferase reporter and RNA pull-down assays confirmed the direct interaction between miR-27a-3p and TET1. In vivo, a subcutaneous xenograft model was used to assess the effect of miR-27a-3p antagomir on tumor growth via tail vein injection. RESULTS: miR-27a-3p was upregulated in HCC tissues, correlating with poor survival, TNM stage, tumor size, alongside vascular invasion. miR-27a-3p knockdown diminished HCC cell growth while promoting apoptosis. Mechanistically, miR-27a-3p targeted TET1. Rescue experiments reflected that TET1 inhibition partially reversed the tumor-suppressive impacts of miR-27a-3p silencing. Further, miR-27a-3p knockdown enhanced p53 levels via TET1, whereas its overexpression suppressed both TET1 and p53. In vivo, miR-27a-3p antagomir suppressed HCC xenograft tumor growth. CONCLUSION: Downregulation of miR-27a-3p exerts a tumor-suppressive impact in HCC by inhibiting malignant biological behaviors, potentially via the TET1/p53 axis.