Abstract
Melanoma is an aggressive malignant tumor. The crucial role of circular RNAs has been documented in many types of cancer, including melanoma. The objective of this study was to uncover the function of circ_0084043 in the biological process of melanoma and associated mechanism of action. The expression of circ_0084043, miR-31, and Krüppel-like factor 3 (KLF3) was determined by qRT-PCR. Cell proliferation and apoptosis were monitored by the MTT assay and flow cytometry assay, respectively. The progression of glycolysis was evaluated according to the levels of glucose consumption, lactate production, and ATP concentration using appropriate detection kits. The relationship between miR-31 and circ_0084043 or KLF3 was predicted by the bioinformatics tool and ascertained by the dual-luciferase reporter assay. The protein levels of KLF3 and glucose transporter 1 (Glut1) were quantified by western blot. A xenograft model was established to ascertain the role of circ_0084043 in vivo. As a result, circ_0084043 expression was reinforced in melanoma tissues and cells. Circ_0084043 knockdown inhibited cell proliferation, induced cell apoptosis, and restrained glycolysis. MiR-31 was a target of circ_0084043, and miR-31 deficiency reversed the role of circ_0084043 knockdown. KLF3 was targeted by miR-31, and KLF3 upregulation abolished the effects of miR-31 enrichment. Moreover, circ_0084043 knockdown impeded tumor growth in vivo and suppressed the level of Glut1 by modulating miR-31 and KLF3. Circ_0084043 promoted cell proliferation and glycolysis, and blocked apoptosis through the circ_0084043–miR-31–KLF3 regulatory axis in melanoma.
Highlights
Melanoma, originating from the malignant transformation of melanocytes, is the most massive malignant tumor in a number of skin cancer–related deaths [1,2]
These analyses suggested that circ_0084043 knockdown impaired proliferation and glycolysis but promoted apoptosis in melanoma cells
We found that miR-31 mimic significantly decreased the luciferase activity in A375 and A875 cells introduced with WT-Krüppel-like factor 3 (KLF3) 3′-UTR but not with MUT-KLF3 3′-UTR (Figure 4b and c)
Summary
Melanoma, originating from the malignant transformation of melanocytes, is the most massive malignant tumor in a number of skin cancer–related deaths [1,2]. Despite significant advances in the diagnosis and treatment with molecular-targeted therapies and immunotherapy in recent years [5,6], the prognosis of melanoma patients is less than ideal and the 5-year survival rate is tragic [3,7]. Yang et al identified a series of dysregulated circRNAs through the microarray analysis of uveal melanoma tissues and normal tissues, including hsa_ circ_0119873, hsa_circ_0128533, and hsa_circ_0047924 [12]. Wang et al obtained several differently expressed circRNAs from melanoma cells and normal melanocytes by microarray analysis [13]. These data indicated that circRNAs are implicated in the development of melanoma.
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