Many studies confirm that circular RNA (circRNA) plays an important regulatory role in the malignant progression of cancer, including melanoma. However, the role of a novel circRNA, circ_0079593, in melanoma is unclear. The expression levels of circ_0079593 and miR-516b were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was measured by cell counting kit-8 (CCK-8) assay, and cell migration and invasion were evaluated using transwell assay. Meanwhile, western blot (WB) analysis was employed to determine the levels of proliferation and metastasis-related proteins, as well as metabotropic glutamate receptor 3 (GRM3) protein. Furthermore, cell apoptosis was tested by detecting the cell apoptosis rate and Caspase-3 activity. The glucose consumption and lactate production of cells were measured to evaluate cell glucose metabolism. Moreover, dual-luciferase reporter assay and biotin-labeled RNA pull-down assay were used to confirm the interaction between miR-516b and circ_0079593 or GRM3. In addition, mice xenograft models were constructed to explore the effect of circ_0079593 on melanoma tumor growth in vivo. Our results discovered that circ_0079593 was highly expressed in melanoma, and its silencing suppressed melanoma cell proliferation, migration, invasion, glucose metabolism and promoted apoptosis. Moreover, we found that circ_0079593 could serve as a sponge of miR-516b, and miR-516b could target GRM3 in melanoma. The rescue experiments revealed that both miR-516b inhibitor and GRM3 overexpression could reverse the inhibition effect of circ_0079593 knockdown on melanoma progression. Additionally, in vivo experiments also revealed that circ_0079593 interference suppressed melanoma tumor growth. Our study concluded that circ_0079593 accelerated melanoma progression via upregulating GRM3 by sponging miR-516b, which suggested that circ_0079593 had the potential to be a new therapeutic biomarker for melanoma.

许多研究证实，环状RNA（circRNA）在包括黑色素瘤在内的癌症恶性进展中起着重要的调节作用。但是，尚不清楚新型circRNA circ_0079593在黑色素瘤中的作用。通过定量实时聚合酶链反应（qRT-PCR）检测到circ_0079593和miR-516b的表达水平。通过细胞计数试剂盒8（CCK-8）测定法测量细胞增殖，并使用transwell测定法评估细胞迁移和侵袭。同时，采用western blot（WB）分析来确定增殖和转移相关蛋白以及代谢型谷氨酸受体3（GRM3）蛋白的水平。此外，通过检测细胞凋亡率和Caspase-3活性来测试细胞凋亡。测量细胞的葡萄糖消耗和乳酸产生以评估细胞葡萄糖代谢。此外，使用双荧光素酶报告基因测定法和生物素标记的RNA下拉测定法来确认miR-516b与circ_0079593或GRM3之间的相互作用。此外，建立小鼠异种移植模型以探索circ_0079593对体内黑色素瘤肿瘤生长的影响。我们的结果发现，circ_0079593在黑色素瘤中高表达，其沉默抑制了黑色素瘤细胞的增殖，迁移，侵袭，葡萄糖代谢并促进了细胞凋亡。此外，我们发现circ_0079593可以充当miR-516b的海绵，而miR-516b可以靶向黑色素瘤中的GRM3。救援实验表明，miR-516b抑制剂和GRM3的过量表达均可逆转circ_0079593敲低对黑素瘤进展的抑制作用。此外，体内实验还显示circ_0079593干扰抑制了黑素瘤肿瘤的生长。我们的研究得出结论，circ_0079593通过使miR-516b海绵化而通过上调GRM3来加速黑色素瘤的进展，这表明circ_0079593有潜力成为黑色素瘤的新型治疗生物标志物。