Long noncoding RNA LINC00518 acts as a competing endogenous RNA to promote the metastasis of malignant melanoma via miR-204-5p/AP1S2 axis

Cell Death Dis. 2019 Nov 11;10(11):855. doi: 10.1038/s41419-019-2090-3.

Abstract

Long intergenic nonprotein coding RNA 518 (LINC00518) has been shown to promote cancer cell growth and metastasis in some human tumors. Although it has been reported that LINC00518 is dysregulated in melanoma, its exact role and molecular mechanism in melanoma remain unclear. RNA-seq analysis and qRT-PCR was used to detect the expression of LINC00518 in melanoma tissues. Melanoma cases from The Cancer Genome Atlas (TCGA), GEO#GSE15605 and GEO#GSE24469 were included in this study. 3D migration, transwell and scratch wound assay were used to explore the role of LINC00518 in melanoma cells. Bioinformatics, luciferase reporter assays, MS2-RIP assay, RNA pull-down assay and RNA-ChIP assay were used to demonstrate the mechanism of LINC00518 in melanoma. We found that LICN00518 was significantly upregulated in melanoma tissue, and high LICN00518 level was an independent risk factor for melanoma patients. LICN00518 promoted the invasion and migration of melanoma cells. LICN00518 exerted its role by decoying miR-204-5p to upregulate Adaptor Related Protein Complex 1 Sigma 2 Subunit (AP1S2) expression. We also demonstrated that LICN00518 promoted melanoma metastasis in vivo through pulmonary metastasis assay. This result elucidates a new mechanism for LICN00518 in the metastasis of melanoma. LICN00518 may serve as a survival indicator and potential therapeutic target in melanoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex sigma Subunits / genetics*
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • RNA, Long Noncoding / genetics*

Substances

  • AP1S2 protein, human
  • Adaptor Protein Complex sigma Subunits
  • MIRN204 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA LINC00518, human