Nuclear miR-3920 expression in hepatocellular carcinoma is associated with stemness marker expression and poorer prognosis

Abstract

Background: Stemness-related marker expression in hepatocellular carcinomas (HCC) has been associated with aggressive behavior. The association between miRNA expression and HCC stemness remains unclear. Aims: To identify miRNAs associated with stemness marker expression in HCC and their clinical significance. Methods: MicroRNA microarray analysis was performed to identify microRNAs that were differentially expressed between EpCAM-positive and EpCAM-negative HCCs. The subcellular localization and expression level of miR-3920 was evaluated by locked nucleic acid-in situ hybridization analysis on surgically resected HCCs and paired non-tumor liver (NT). Results: There was significant upregulation of miR-3920 in EpCAM-positive HCCs compared to EpCAMnegative cases ( p = 0.025). Nuclear miR-3920 expression ( p < 0.001) and the nuclear-to-total miR-3920 signal ratio ( p < 0.001) were significantly higher in HCCs compared with NT. High nuclear-to-total miR3920 signal ratio was positively correlated with stemness marker expression (EpCAM, p = 0.002; K19, p < 0.001), the presence of microvascular invasion ( p = 0.004), major vessel invasion ( p = 0.001) and mitosis ( p < 0.001). Higher nuclear-to-total miR-3920 signal ratio was associated with significantly decreased overall survival ( p = 0.010) and disease-free survival ( p = 0.016). Conclusion: Increased expression of miR-3920 in the nuclei of HCC tumor cells was associated with stemness-related marker expression and aggressive clinicopathological features of HCC, suggesting a possible role for miR-3920 in HCC stemness and progression. (c) 2025 The Author(s). Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )