Circ_0079593 facilitates proliferation, metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating
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Circ_0079593 facilitates proliferation, metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating the miR‑516b/ GRM3 axis Jiajing Lu1 · Ying Li1 Received: 1 March 2020 / Accepted: 7 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Melanoma · circ_0079593 · miR-516b · GRM3 Abbreviations qRT-PCR Quantitative real-time polymerase chain reaction CCK-8 Cell counting kit-8 GRM3 Metabotropic glutamate receptor 3
* Jiajing Lu [email protected] 1
Department of Dermatology, Shanghai Skin Disease Hospital, No. 1278 Baode Road, Jing′an District, Shanghai 200443, China
Introduction Melanoma is the most deadly form of skin cancer, with high malignancy, early metastasis and high mortality [1, 2]. The occurrence of malignant melanoma is due to the proliferation of melanocytes, mainly manifested by skin bleeding, itching, tenderness, and ulcers [3, 4]. Although the etiology of melanoma is not fully understood, genetics and environment are considered to be important risk factors for melanoma [5, 6]. Surgical t
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