Objective: Human uveal melanoma (UM) is a common ocular malignant tumor with a high risk of metastasis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are correlated with the development of UM. Here, we aimed to determine the biological significance of lncRNA growth arrest-specific transcript 5 (GAS5) in UM.
Methods: The expression levels of GAS5 and microRNA-21 (miR-21) in UM tissues and cells were detected by qRT-PCR analysis. CCK-8 assay was performed to investigate the viability of UM cells after cell transfections, and the migration and invasion of UM cells were determined by transwell assay. The protein expression levels were detected by Western blot assay. The relationship between miR-21 and GAS5 in UM cells was confirmed by bioinformatics prediction and luciferase report assay.
Results: Our experiments demonstrated that GAS5 was markedly downregulated in UM cells and clinical specimens. Overexpression of GAS5 inhibited, whereas knockdown of GAS5 promoted the viability, migration, and invasion of UM cells. The epithelial-to-mesenchymal transition (EMT) process of UM cells was also suppressed by upregulating of GAS5 and enhanced by downregulating of GAS5. Additionally, as a competitive endogenous RNA (ceRNA), GAS5 directly binded to the oncogenic miR-21 in UM cells, and overexpression of miR-21 attenuated the EMT-suppressing effect of GAS5.
Conclusion: Taken together, our findings suggest that GAS5/miR-21 axis is implicated in the pathogenesis of UM and might serve as a potential therapeutic target.
Keywords: GAS5, uveal melanoma, invasion, epithelial–mesenchymal transition, microRNA-21