LINC00518 Promotes Cell Malignant Behaviors via Influencing EIF4A3-Mediated mRNA Stability of MITF in Melanoma

Abstract

Melanoma has become the most severe sort of skin cancer, deriving from the pigment-producing melanocytes. Existing research has validated that long noncoding RNAs (lncRNAs) have critical function in the progression of cancers. LINC00518 has been studied in cutaneous melanoma; however, the molecular mechanism of LINC00518 in melanoma needs in-depth investigation. In our study, LINC00518 was revealed to be upregulated in melanoma tissues and cells, and melanoma patients in high LINC00518 expression group had poorer prognosis as depicted in GEPIA database. Functional assays revealed that LINC00518 depletion inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, MITF was confirmed to be upregulated in melanoma tissues and cells, and melanoma patients in high MITF expression group had poorer prognosis as displayed in GEPIA database. MITF expression was positively connected to LINC00518 expression. Additionally, results of mechanism assays uncovered EIF4A3 could bind with LINC00518 and MITF, and LINC00518 recruited EIF4A3 to stabilize MITF mRNA. Finally, it was demonstrated that upregulation of MITF could partially abrogate the inhibitory impact of LINC00518 knockdown on melanoma cell malignant behaviors. To summarize, LINC00518 promotes the malignant processes of melanoma cells through targeting EIF4A3/MITF axis, which might provide novel potential biomarkers for melanoma prognosis.