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

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 EpCAM-negative 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 miR-3920 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.