<p>Long Noncoding RNA CCAT1 Functions as a Competing Endogenous RNA to Upregulate ITGA9 by Sponging MiR-296-3p in Melanoma</p>

Abstract

Background: Melanoma is aggressive and lethal melanocytic neoplasm, and its incidence has increased worldwide in recent decades. Accumulating evidence has showed that various long noncoding RNAs (lncRNAs) participated in occurrence of malignant tumors, including melanoma. The present study was designed to investigate function of lncRNA colon cancerassociated transcript-1 (CCAT1) in melanoma. Methods: The expression levels of CCAT1, miR-296-3p and Integrin alpha9 (ITGA9) in melanoma tissues or cells were measured using real-time quantitative polymerase chain reaction (RT-qPCR). The concentrations of glucose and lactate were measured for assessing glycolysis of melanoma cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), flow cytometry, and transwell assays were conducted to assess proliferation, apoptosis, and migration of melanoma cells. Western blot assay was performed to measure the protein expression of ITGA9, hexokinase 2 (HK2), and epithelial-mesenchymal transition (EMT)-related proteins in melanoma tissues or cells. The relationship among CCAT1, miR-296-3p, and ITGA9 was predicted and confirmed by bioinformatics analysis, dualluciferase reporter, and RNA immunoprecipitation (RIP) assay, respectively. A xenograft experiment was established to assess the effect of CCAT1 knockdown in vivo. Results: CCAT1 was effectively increased in melanoma tissues and cells compared with matched controls, and deficiency of CCAT1 impeded cell glycolysis, proliferation, migration while induced apoptosis, which were abrogated by knockdown of miR-296-3p in melanoma cells. In addition, our findings revealed that ITGA9 overexpression abolished miR-296-3p overexpression-induced effects on melanoma cells. Importantly, CCAT1 regulated ITGA9 expression by sponging miR-296-3p. The results of xenograft experiment suggested that CCAT1 silencing inhibited melanoma cell growth in vivo. Conclusion: LncRNA CCAT1 promoted ITGA9 expression by sponging miR-296-3p in melanoma.

Identification of Therapeutic Targets and Prognostic Biomarkers Among Integrin Subunits in the Skin Cutaneous Melanoma Microenvironment

“…ITGA9 is a host gene for various long non-coding RNAs, including LncCCAT1 and HOXA11-AS. Therefore, proliferation, apoptosis, metastasis of melanoma cells may be modulated via regulation of ITGA9 -related non-coding RNAs ( 46 , 47 ). In the present study ITGA9 was positively correlated with the invasion of several immune cells in SKCM TIME, but not tumor purity ( Figure 7 ).…”

[Retracted] circZC3HAV1 Regulates TBC1D9 to Affect the Biological Behavior of Colorectal Cancer Cells

“…This assay was performed as previously described [ 18 ]. Using Magna RIP RNA-Binding Protein Immunoprecipitation Kit, RIP assay was carried out.…”

Regulation of LncRNAs in Melanoma and Their Functional Roles in the Metastatic Process

“…Notably, SAMMSON expression is required for melanoma growth in vivo and in vitro and confers resistance to MAPK inhibitors [97,98]. The lncRNAs H19 and CCAT1, instead, control melanoma cell invasion in vitro and tumor growth in vivo by regulating glucose metabolism [99][100][101]. The lncRNA LINC00518 directly regulates levels of the hypoxia-inducible factor HIF1α and glucose consumption in melanoma cells and promotes melanoma invasion, tumor growth, and radio-resistance in mice xenografts [102].…”