Long non-coding RNAs (lncRNAs) regulate gene expression and play a significant role in cancer progression. Previously, downregulation of lncRNA MEG3 was shown to associate with poor clinical outcomes in melanoma patients. The basis for this association has not been described and the aims of this study were to identify a role for lncRNA MEG3 in melanoma and to describe its regulatory mechanism of action. RT-qPCR was used to detect lncRNA MEG3 expression in melanoma cells and tissues. Luciferase reporter assays were used to identify lncRNA MEG3 downstream targets. Melanoma cells were transfected with various expression vectors and these transfected cells were assessed for; migration, colony formation, proliferation, in vivo tumorigenesis, and metastatic potential. Melanoma cell lines were found to be sensitive to lncRNA MEG3 expression levels and overexpression was found to inhibit melanoma cell proliferation and invasion, both in vitro and in vivo. Luciferase reporter assays identified miR-208 and SOX4 as downstream targets of lncRNA MEG3. Overexpression of miR-208 and silencing of SOX4 rescued invasion and proliferation by cells that overexpressed lncRNA MEG3. Moreover, lncRNA MEG3 inhibited cancer stem cell differentiation and suppressed melanoma progression and metastasis through inhibition of miR-208 by SOX4.
Keywords: LncRNA MEG3; Melanoma; Metastasis; Proliferation; miR-208.
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