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OBJECT To investigate the role of circHIPK3 in melanoma. METHODS Bioinformatics analysis and experiments including RT-qPCR, Pearson's correlation analysis, luciferase reporter, Western blot, and RIP assays were applied to explore the function and mechanism of circHIPK3 in melanoma. RESULTS CircHIPK3 expression was strikingly upregulated while miR-215-5p was downregulated in melanoma tissues and cell lines. Pearson's correlation analysis unveiled circHIPK3 expression was positively correlated with Ki-67 (a marker of proliferation), which implied that circHIPK3 may play a vital role in the progression of melanoma. In mechanism, luciferase reporter and RIP assays validated that circHIPK3 was able to bind with miR-215-5p. Moreover, we confirmed that overexpression of circHIPK3 could facilitate cell proliferation and depress cell apoptosis in melanoma while overexpression of miR-215-5p exerted opposite effects. Besides, our findings indicated that miR-215-5p overexpression significantly reversed the circHIPK3 overexpressing-mediated promotive effect on cell proliferation and inhibitory effect on cell apoptosis. Furthermore, we found that miR-215-5p could directly target YY1. Upregulation of YY1 could notably offset the inhibitory effect of circHIPK3 downregulation on cell proliferation and the promotive effect on cell apoptosis. CONCLUSION Our study corroborated that circHIPK3 regulated melanoma cell behaviors via the miR-215-5p/YY1 axis, which might provide a novel insight for the treatment of melanoma patients.