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环状 RNA_0084043 通过 miR-153-3p/Snail 轴促进恶性黑素瘤进展。

circRNA_0084043 promote malignant melanoma progression via miR-153-3p/Snail axis.

机构信息

Department of Plastic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.

Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Biochem Biophys Res Commun. 2018 Jul 7;502(1):22-29. doi: 10.1016/j.bbrc.2018.05.114. Epub 2018 May 19.

DOI:10.1016/j.bbrc.2018.05.114
PMID:29777697
Abstract

Circular RNAs (circRNAs) has been found to play an important role in the regulation of multiple diseases, and participate in cancer development. However, the role of circRNA in malignant melanoma has not been reported. In this study, human circRNA microarray was used to screen the dysregulated circRNA in melanoma. We found that circRNA_0084043 was significantly up-regulated in melanoma tissue, and the result was replicated in a larger sample size. High circRNA_0084043 expression was an independent risk factor of overall survival in melanoma patients. circRNA_0084043 promotes melanoma cell proliferation, invasion and migration. Bioinformatics and luciferase reporter assays confirmed that circRNA_0084043 directly binds to miR-153-3p, and Snail is directly targeted by miR-153-3p. We also demonstrated that circRNA_0084043 may act as the sponge of miR-153-3p to up-regulate Snail expression, and consequently function as an oncogene in melanoma. Overall, this result elucidates a new mechanism for circRNA_0084043 in melanoma development and provides a potential therapeutic target for melanoma patients.

摘要

环状 RNA(circRNAs)已被发现在多种疾病的调控中发挥重要作用,并参与癌症的发生。然而,circRNA 在恶性黑色素瘤中的作用尚未见报道。在本研究中,我们使用人类环状 RNA 微阵列筛选了黑色素瘤中失调的环状 RNA。我们发现 circRNA_0084043 在黑色素瘤组织中显著上调,并且在更大的样本量中得到了验证。circRNA_0084043 的高表达是黑色素瘤患者总生存的独立危险因素。circRNA_0084043 促进黑色素瘤细胞的增殖、侵袭和迁移。生物信息学和荧光素酶报告基因实验证实 circRNA_0084043 可直接与 miR-153-3p 结合,而 Snail 是 miR-153-3p 的直接靶标。我们还表明,circRNA_0084043 可能作为 miR-153-3p 的海绵来上调 Snail 表达,并因此在黑色素瘤中发挥癌基因的作用。总之,该结果阐明了 circRNA_0084043 在黑色素瘤发生发展中的新机制,并为黑色素瘤患者提供了潜在的治疗靶点。

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