环状RNAcirc_0051277竞争性结合miR-1193调控c-MYC影响恶性黑色素瘤谷氨酰胺和脯氨酸代谢的机制研究

氨基酸代谢在黑色素瘤的恶性进展中发挥了重要作用。我们发现：circ_0051277在恶性黑色素瘤中高表达；下调circ_0051277及c-MYC可抑制黑色素瘤细胞谷氨酰胺和脯氨酸代谢及生长；circ_0051277和c-MYC的3’UTR区存在miR-1193结合位点，miR-1193靶向抑制c-MYC，circ_0051277结合miR-1193；过表达circ_0051277不影响miR-1193表达，却促进其靶基因c-MYC的表达。据此提出假说：circ_0051277竞争性结合miR-1193促进c-MYC调控恶性黑色素瘤谷氨酰胺和脯氨酸代谢。本课题建立circ_0051277、miR-1193、c-MYC不同表达状态的细胞模型并进行细胞代谢实验，结合非编码RNA间调控和转录后调控研究，探讨三者在黑色素瘤谷氨酰胺和脯氨酸代谢中的作用机制，为恶性黑色素瘤分子诊断和靶向治疗提供依据。

Amino acid metabolism plays an important role in the malignant progression of melanoma. We found that circ_0051277 is overexpressed in malignant melanoma tissues and cells. Down-regulation of circ_0051277 and c-MYC inhibited the glutamine and proline metabolism and growth of malignant melanoma cell. There are miR-1193 binding sites on the binding sites on the circ_0051277 and 3’-UTR of c-MYC. GLS is the direct functional target of miR-1193, circ_0051277 can combined with miR-1193. Overexpression of circ_0051277 did not affect the expression of miR-1193, but promoted the c-MYC expression. Thus, we proposed the hypothesis that circRNA circ_0051277 influence the glutamine and proline metabolism of malignant melanoma through regulating c-MYC by sponging miR-1193. In the future study, we will intend to establish circ_0051277/miR-1193/c-MYC diverse expression of cell model and take a serial of cell metabolism experiments, combined with noncoding RNA regulation and post-transcriptional regulation research, evaluate the effect of circ_0051277/miR-1193/c-MYC pathway on the malignant melanoma glutamine and proline metabolism. We further analyze the role of key notes in molecular diagnosis and targeting therapy of malignant melanoma.