Circ_0079593 facilitates proliferation, metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating the miR-516b/GRM3 axis.

Abstract

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.