LncRNA MEG3 inhibits retinoblastoma invasion and metastasis by inducing β-catenin degradation.

In our previous study, we found that low expression of LncRNA-MEG3 was closely associated with the invasion and metastasis of retinoblastomas. The molecular mechanism by which MEG3 inactivation induces the invasion and metastasis of retinoblastoma cell lines remains unclear. We used the GEO database to analyze the expression of MEG3 in retinoblastoma tissues and MEG3-related pathways. The scratch, transwell migration, mouse tumor metastasis, and mouse fluorescence live imaging assays were performed to detect migration and invasion of retinoblastoma cell lines. The RNA pull down, electrophoretic mobility shift, RIP, co-immunoprecipitation, and ubiquitination assays were performed to analyze the molecular mechanisms. The GEO database showed that the expression of MEG3 was low in retinoblastoma tissues and was closely associated with the invasion of retinoblastoma cells and activity of the Wnt pathway. Both and experiments confirmed that MEG3 inhibited the migration and invasion of retinoblastoma cells. Cell experiments confirmed that MEG3 could promote the binding of β-catenin and GSK-3β and induce phosphorylation, ubiquitination and degradation of β-catenin indirectly. In conclusion, MEG3 can promote the degradation of β-catenin via GSK-3β, which in turn inactivates the Wnt pathway and ultimately inhibits the invasion and metastasis of retinoblastoma cells.