CircRTTN upregulates EPHA2 to aggravate the malignant process of melanoma via sponging miR-890

Abstract

Background. Malignant melanoma is a kind of tumor derived from melanocytes, which has the characteristics of drug resistance and distant metastasis. Accumulating evidence has demonstrated that circular RNAs (circRNAs) are involved in the pathogenesis of melanoma. Our current study aimed to investigate the role and mechanism of circRTTN in melanoma progression. Methods. The levels of circRTTN, microRNA-890 (miR-890) and EPH receptor A2 (EPHA2) were examined via quantitative real-time PCR (qRT-PCR) and Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2’-deoxyuridine (EdU) staining, flow cytometry, transwell and tube formation assays were conducted to estimate the effects of circRTTN on growth, apoptosis, migration, invasion and angiogenesis of melanoma cells. Western blot was used to measure related marker protein levels. The interaction between miR-890 and circRTTN or EPHA2 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circRTTN in vivo. Results. CircRTTN and EPHA2 levels were upregulated, while miR-890 was down-regulated in melanoma tissues and cells. CircRTTN knockdown restrained cell proliferation, migration, invasion and angiogenesis, but promoted cell apoptosis in vitro. CircRTTN was an effective molecular sponge for miR890, and negatively regulated miR-890 expression. The suppressive role of circRTTN knockdown on cell growth, metastasis and angiogenesis in vitro was abated by blocking miR-890. MiR-890 directly targeted EPHA2. MiR-890 overexpression elicited a similar antitumor role in melanoma cells, which was abrogated by overexpression of EPHA2. In addition circRTTN knowdown markedly attenuated xenograft tumor growth in vivo. Conclusion. Our findings demonstrated that circRTTN mediated melanoma progression via regulating the miR-890/ EPHA2 axis.