<p>Long Noncoding RNA <em>LINC00173</em> Promotes the Malignancy of Melanoma by Promoting the Expression of IRS4 Through Competitive Binding to microRNA-493</p>
Fan Yang, Pengzhen Lei, Weihui Zeng, Jianwu Gao, Na Wu
Abstract
Purpose: Long intergenic non-protein-coding RNA 173 ( LINC00173 ) plays crucial roles in lung cancer. However, the expression and biological functions of LINC00173 in melanoma have not yet been investigated. In this study, we aimed to characterize the involvement of LINC00173 in melanoma and elucidate its mechanisms of action. Materials and Methods: Reverse-transcription quantitative PCR was performed to measure LINC00173 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 LINC00173 was upregulated in melanoma tissues and cell lines. High LINC00173 expression was closely associated with TNM stage, lymph node metastasis, and shorter overall survival of patients with melanoma. Functional assays revealed that LINC00173 downregulation inhibited melanoma cell proliferation, migration, and invasion and induced apoptosis, suggesting that LINC00173 acts as an oncogenic RNA. LINC00173 knockdown retarded the tumorous growth of melanoma cells in vivo. Mechanistically, LINC00173 increased insulin receptor substrate 4 (IRS4) expression by sponging microRNA-493 (miR-493), thereby acting as a competing endogenous RNA. The effects of LINC00173 knockdown on the malignant phenotype of melanoma cells were reversed by overexpression of IRS4 or knockdown of miR-493. Conclusion: The LINC00173 –miR-493–IRS4 pathway regulates melanoma characteristics by increasing the expression of IRS4 via competitive binding of LINC00173 to miR-493, suggesting that this pathway is a potential target for the diagnosis, prognosis, and/or treatment of melanoma. Keywords: LINC00173 , miR-493, melanoma, therapeutic target