Skin cutaneous melanoma (SKCM) is one of the most aggressive and life-threatening cancers with high incidence rate, metastasis rate and mortality.,Early detection and stratification of risk assessment are essential to treat SKCM and to improve survival rate.,The aim of this study is to construct an immune-related lncRNAs (immlncRNAs) prognosis risk model to identify immune biomarkers for early diagnosis, prognosis assessment and target immunotherapy of SKCM.,For this purpose, we identified 46 immlncRNAs significantly correlated with SKCM prognosis to construct the prognostic risk model and patients were stratified into the high- and low-risk subgroups according to the developed model.,The predictive efficiency of this model has been proved by K-M survival analysis and receiver operating characteristic curve.,Moreover, CIBERSORT algorithms confirmed that there were differences in immune cell infiltration between the high- and low-risk groups.,Functional enrichment analysis further indicated that immlncRNAs were related to a variety of immune response process signaling pathways, suggesting that relevant immlncRNAs could play an important role in the immune regulation of SKCM.,Finally, subgroup analysis and multiple Cox regression analysis further proved the stability of the model.,In summary, we successfully constructed a 46 immlncRNA-related prognostic risk score model with excellent predictive efficacy and provided more possibilities to investigate the immune regulation mechanisms and to develop immunotherapy of SKCM.
The abnormal expression of long noncoding RNA- (lncRNA-) MEG3 was clearly identified in a number of malignant tumors, but the specific function of MEG3 remains unknown in malignant melanoma until now.,The research attempts to explore the effects of MEG3 on the growth and metastasis of malignant melanoma.,MEG3 and miR-499-5p expression were determined by qRT-PCR method.,Western blotting assay was applied to detect protein expression.,Luciferase reporter assay was used to assess the correlation between MEG3 and miR-499-5p and between CYLD and miR-499-5p.,Cell growth, cell cycle, and cell apoptosis were examined by CCK-8 assay, EdU assay, and flow cytometry assay, respectively.,The invasion ability of melanoma cells was investigated by wound-healing and Transwell assays.,The effect of MEG3 on growth of melanoma in vivo and cell chemosensitivity was detected by xenograft animal model and CCK-8 assay.,As a result, the expression of MEG3 was decreased in melanoma tissues and cell lines.,The level of MEG3 was significantly associated with poor prognosis.,MEG3 could bind to miR-499-5p and CYLD mRNA contained a binding site of miR-499-5p.,The expression of CYLD was reduced and the level of miR-499-5p was elevated in melanoma tissues and cell lines.,Luciferase reporter assay and western blot assay confirmed that MEG3 regulated the expression of CYLD by sponging miR-499-5p.,Functionally, upregulation of MEG3 inhibited melanoma cell proliferation, invasion, and migration, enhanced melanoma cell apoptosis, arrested melanoma cell cycle, and regulated the expression of E-cadherin, N-cadherin, and cyclin D1 by regulating CYLD expression mediated by sponging miR-499-5p.,Importantly, overexpression of MEG3 suppressed the growth of xenograft tumor and improved chemotherapy sensitivity of A375 cells to cisplatin and 5-FU treatment.,In conclusion, MEG3 has a crucial function in the tumorigenesis of melanoma, and MEG3 may be a potential therapeutic target in the treatment of melanoma.