Upregulation of the lncRNA MEG3 in Metastatic Hepatoblastoma

Hepatoblastoma is the most common 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 investigated the expression and functional significance of the lncRNA, maternally expressed gene 3 (MEG3), in a metastatic model of hepatoblastoma. RNA sequencing compared the metastatic hepatoblastoma cell line HLM_2 with its parental HuH6 cell line to identify differentially expressed lncRNAs. MEG3 expression was examined using hepatoblastoma patient datasets and validated using qPCR in cell lines, orthotopic tumors, and COA67 patient-derived xenografts. Functional effects of MEG3 knockdown in HLM_2 cells were evaluated with siRNA to evaluate clonogenicity, tumorsphere formation, migration, and invasion. The effects of MEG3 overexpression on clonogenicity, migration, and invasion were assessed in HuH6 cells. MEG3 was significantly upregulated in metastatic cells and orthotopic tumors compared with controls. MEG3 silencing reduced clonogenicity, tumorsphere formation, migration, and invasion. MEG3 overexpression increased clonogenicity, migration, and invasion. These findings indicate that MEG3 is upregulated in metastatic hepatoblastoma and may contribute to aggressive tumor phenotype, warranting further examination of the mechanistic role of MEG3 in hepatoblastoma, and its relevance as a biomarker or therapeutic target.