# Upregulation of the lncRNA MEG3 in Metastatic Hepatoblastoma

## TL;DR

The lncRNA MEG3 is upregulated in metastatic liver cancer in children and promotes aggressive tumor behavior.

## Contribution

MEG3 is identified as an oncogenic lncRNA in metastatic hepatoblastoma, with functional roles in tumor progression.

## Key findings

- MEG3 is consistently upregulated in metastatic hepatoblastoma across multiple models and patient datasets.
- Silencing MEG3 reduces tumor cell clonogenicity, stemness, and motility, while overexpression enhances motility.
- MEG3 contributes to aggressive tumor phenotypes and may serve as a potential biomarker or therapeutic target.

## Abstract

What are the main findings?
The lncRNA MEG3 is consistently upregulated in metastatic hepatoblastoma across cell lines, orthotopic tumors, PDX models, and patient datasets.MEG3 promotes aggressive tumor phenotypes, as its silencing reduces clonogenicity, stemness, and motility, while its overexpression enhances motility.

The lncRNA MEG3 is consistently upregulated in metastatic hepatoblastoma across cell lines, orthotopic tumors, PDX models, and patient datasets.

MEG3 promotes aggressive tumor phenotypes, as its silencing reduces clonogenicity, stemness, and motility, while its overexpression enhances motility.

What are the implications of the main findings?
MEG3 appears to function as an oncogenic lncRNA in hepatoblastoma, differing from its role in other malignancies.These findings suggest that MEG3 may be involved in pathways associated with hepatoblastoma progression and metastasis.

MEG3 appears to function as an oncogenic lncRNA in hepatoblastoma, differing from its role in other malignancies.

These findings suggest that MEG3 may be involved in pathways associated with hepatoblastoma progression and metastasis.

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 (MEG3), in a metastatic hepatoblastoma model. RNA sequencing comparing the metastatic hepatoblastoma cell line, HLM_2, with its parental HuH6 cell line identified MEG3 as being significantly upregulated in metastatic cells. MEG3 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 MEG3 knockdown in HLM_2 cells on clonogenicity, migration, and invasion were evaluated. The effects of MEG3 overexpression on 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 migration and invasion. These findings indicate that MEG3 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.