lncRNA-MEG3 Suppresses the Proliferation and Invasion of Melanoma by Regulating CYLD Expression Mediated by Sponging miR-499-5p.
lncRNA-MEG3 Suppresses the Proliferation and Invasion of Melanoma by Regulating CYLD Expression Mediated by Sponging miR-499-5p.
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DOI：
10.1155/2018/2086564
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发表时间：
2018
影响因子：
--
通讯作者：
Pi X
中科院分区：
文献类型：
--
作者：
Long J;Pi X
MEG3在多种恶性肿瘤中都有明显的异常表达，但MEG3在恶性黑色素瘤中的具体功能尚不清楚。本研究试图探讨MEG3对恶性黑色素瘤生长和转移的影响。用qRT-PCR方法检测MEG3和miR-499-5p的表达。Western blotting检测蛋白表达。用荧光素酶报告法检测MEG3与miR-499-5p、CyLD与miR-499-5p的相关性。采用CCK-8比色法、EDU比色法和流式细胞仪分别检测细胞生长、细胞周期和细胞凋亡。用创面愈合实验和Transwell实验检测黑色素瘤细胞的侵袭能力。采用异种移植动物模型和CCK-8法检测MEG3对黑色素瘤的体内生长和细胞化疗敏感性的影响。结果，MEG3在黑色素瘤组织和细胞系中的表达减少。MEG3水平与预后不良密切相关。MEG3能与miR-499-5P结合，而CyLD mRNA含有miR-499-5P的结合部位。在黑色素瘤组织和细胞系中，CyLD的表达降低，miR-499-5p的表达升高。荧光素酶报告实验和免疫印迹实验证实，MEG3通过海绵化miR-499-5p调控CyLD的表达。在功能上，MEG3的上调抑制了黑色素瘤细胞的增殖、侵袭和迁移，促进了黑色素瘤细胞的凋亡，阻止了黑色素瘤细胞周期，并通过海绵miR-499-5p调节CyLD的表达，调节了E-钙粘蛋白、N-钙粘蛋白和细胞周期蛋白D1的表达。重要的是，MEG3的过表达抑制了移植瘤的生长，并提高了A375细胞对顺铂和5-FU的化疗敏感性。综上所述，MEG3在黑色素瘤的发生发展过程中起着至关重要的作用，MEG3可能成为治疗黑色素瘤的潜在靶点。
The abnormal expression of long noncoding RNA- (lncRNA-) MEG3 was clearly identified in a number of malignant tumors, but the specific function of MEG3 remains unknown in malignant melanoma until now. The research attempts to explore the effects of MEG3 on the growth and metastasis of malignant melanoma. MEG3 and miR-499-5p expression were determined by qRT-PCR method. Western blotting assay was applied to detect protein expression. Luciferase reporter assay was used to assess the correlation between MEG3 and miR-499-5p and between CYLD and miR-499-5p. Cell growth, cell cycle, and cell apoptosis were examined by CCK-8 assay, EdU assay, and flow cytometry assay, respectively. The invasion ability of melanoma cells was investigated by wound-healing and Transwell assays. The effect of MEG3 on growth of melanoma in vivo and cell chemosensitivity was detected by xenograft animal model and CCK-8 assay. As a result, the expression of MEG3 was decreased in melanoma tissues and cell lines. The level of MEG3 was significantly associated with poor prognosis. MEG3 could bind to miR-499-5p and CYLD mRNA contained a binding site of miR-499-5p. The expression of CYLD was reduced and the level of miR-499-5p was elevated in melanoma tissues and cell lines. Luciferase reporter assay and western blot assay confirmed that MEG3 regulated the expression of CYLD by sponging miR-499-5p. Functionally, upregulation of MEG3 inhibited melanoma cell proliferation, invasion, and migration, enhanced melanoma cell apoptosis, arrested melanoma cell cycle, and regulated the expression of E-cadherin, N-cadherin, and cyclin D1 by regulating CYLD expression mediated by sponging miR-499-5p. Importantly, overexpression of MEG3 suppressed the growth of xenograft tumor and improved chemotherapy sensitivity of A375 cells to cisplatin and 5-FU treatment. In conclusion, MEG3 has a crucial function in the tumorigenesis of melanoma, and MEG3 may be a potential therapeutic target in the treatment of melanoma.
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影响因子：
6.5
作者：
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