Background
Maternally expressed gene 3 (MEG3) is a long non-coding RNA (lncRNA) and involved in progression of various human tumors. However, its underlying regulatory mechanism in tumorigenesis of bladder cancer (BC) remains unclear. To demonstrate effects of MEG3 on BC cell proliferation and elaborate its regulatory mechanism in BC.
Conclusions
lncRNA MEG3 could function as a competing endogenous RNA of miR-93 to regulate the tumorigenesis of BC via PI3K/AKT/mTOR pathway. The present research provided a new perspective to understanding the pathogenic mechanism of BC, and an effective therapeutic target for BC.
Methods
Aberrant expressions of MEG3 and miR-93-5p were induced by cell transfection. The mRNA and protein expression were analyzed using qRT-PCR and western blot. Cell proliferation was examined by CCK-8 assay and EdU staining. The targeted regulation effect of MEG3 on miR-93-5p was confirmed by luciferase reporter assay. The number of LC3 punctated cells was detected by immunofluorescence. Xeno-graft mouse model was constructed for in vivo validation.
Results
MEG3 was down-regulated with increased expression of miR-93-5p in BC cells and tissues. Luciferase reporter assay showed that miR-93-5p was a direct target of MEG3 and was negatively regulated by MEG3. MEG3 overexpression inhibited cell proliferation and the expression of proliferation-, apoptosis- and autophagy-related proteins. The activation of PI3K/AKT/mTOR pathway was also suppressed with elevated cell apoptosis. miR-93-5p overexpression counteracted these results. In vivo experiments, we confirmed that miR-93-5p overexpression reversed the MEG3 overexpression-mediated suppression on tumor growth and protein expression. Conclusions: lncRNA MEG3 could function as a competing endogenous RNA of miR-93 to regulate the tumorigenesis of BC via PI3K/AKT/mTOR pathway. The present research provided a new perspective to understanding the pathogenic mechanism of BC, and an effective therapeutic target for BC.