Long Noncoding RNA Promotes the Malignancy of Melanoma by Promoting the Expression of IRS4 Through Competitive Binding to microRNA-493.

PURPOSE

Long intergenic non-protein-coding RNA 173 () plays crucial roles in lung cancer. However, the expression and biological functions of in melanoma have not yet been investigated. In this study, we aimed to characterize the involvement of in melanoma and elucidate its mechanisms of action.

MATERIALS AND METHODS

Reverse-transcription quantitative PCR was performed to measure expression in melanoma. A CCK-8 assay, flow cytometry, and migration and invasion assays were applied to examine melanoma cell proliferation, apoptosis, migration, and invasion, respectively. A xenograft tumor experiment was performed to determine the tumorous growth of melanoma cells in vivo.

RESULTS

We found that was upregulated in melanoma tissues and cell lines. High expression was closely associated with TNM stage, lymph node metastasis, and shorter overall survival of patients with melanoma. Functional assays revealed that downregulation inhibited melanoma cell proliferation, migration, and invasion and induced apoptosis, suggesting that acts as an oncogenic RNA. knockdown retarded the tumorous growth of melanoma cells in vivo. Mechanistically, increased insulin receptor substrate 4 (IRS4) expression by sponging microRNA-493 (miR-493), thereby acting as a competing endogenous RNA. The effects of knockdown on the malignant phenotype of melanoma cells were reversed by overexpression of IRS4 or knockdown of miR-493.

CONCLUSION

The -miR-493-IRS4 pathway regulates melanoma characteristics by increasing the expression of IRS4 via competitive binding of to miR-493, suggesting that this pathway is a potential target for the diagnosis, prognosis, and/or treatment of melanoma.