Upregulation of the lncRNA MEG3 in Metastatic Hepatoblastoma

Hepatoblastoma is the predominant primary liver malignancy in children, and outcomes remain poor for patients with metastatic disease. Long non-coding RNAs (lncRNAs) regulate tumor behavior, but their role in metastatic hepatoblastoma is not well defined. This study investigates the expression and functional significance of the lncRNA, maternally expressed gene 3 (<i>MEG3</i>), in a metastatic hepatoblastoma model. RNA sequencing comparing the metastatic hepatoblastoma cell line, HLM_2, with its parental HuH6 cell line identified <i>MEG3</i> as being significantly upregulated in metastatic cells. <i>MEG3</i> expression was examined using hepatoblastoma patient datasets and validated using qPCR in cell lines, orthotopic tumors, and COA67 patient-derived xenografts. The effects of siRNA <i>MEG3</i> knockdown in HLM_2 cells on clonogenicity, migration, and invasion were evaluated. The effects of <i>MEG3</i> overexpression on migration and invasion were assessed in HuH6 cells. <i>MEG3</i> was significantly upregulated in metastatic cells and orthotopic tumors compared with controls. <i>MEG3</i> silencing reduced clonogenicity, tumorsphere formation, migration, and invasion. <i>MEG3</i> overexpression increased migration and invasion. These findings indicate that <i>MEG3</i> contributes to an aggressive tumor phenotype, highlighting the need for further examination into its mechanistic role in hepatoblastoma and its potential as a biomarker or therapeutic target.