Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis

Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis
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长非编码RNA LINC00520通过诱导miR-125b-5p/EIF5A2轴促进恶性黑色素瘤的增殖和转移

DOI:
10.1186/s13046-020-01599-7
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发表时间:
2020-05-28
影响因子:
11.3
通讯作者:
Bu, Xuefeng
Bu, Xuefeng
中科院分区:
医学1区
文献类型:
--
作者:
Luan, Wenkang;Ding, Yuting;Bu, Xuefeng

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长基因间非蛋白编码RNA 520 (LINC00520)是一种新发现的lncRNA,已被证明在一些恶性肿瘤中调节肿瘤细胞的恶性表型。然而,LINC00520在恶性黑色素瘤中的确切作用和分子机制尚未得到研究。方法采用RNA-seq法和qRT-PCR法检测LINC00520在黑色素瘤组织中的表达。来自公共数据库(the Cancer Genome Atlas (TCGA)、GEO#GSE15605、GEO#GSE34460和GEO#GSE24996)的黑色素瘤病例被纳入本研究。采用CCK-8法、EdU法、transwell法和抓伤法探讨LINC00520在黑色素瘤细胞中的作用。采用荧光素酶报告基因检测、MS2-RIP、RNA pull-down和RNA- chip检测验证LINC00520在黑色素瘤中的分子生物学机制。结果我们发现LICN00520在黑色素瘤组织中过表达。LICN00520的高表达是影响黑色素瘤患者预后的危险因素。LINC00520促进黑色素瘤细胞的增殖、侵袭和迁移。LICN00520通过竞争性结合miR-125b-5p促进真核起始因子5A2 (EIF5A2)表达,发挥其致癌作用。我们还发现,LICN00520通过调节miR-125b-5p/EIF5A2轴,在体内促进黑色素瘤的生长和转移。结论上述结果阐明了LINC00520在黑色素瘤恶性发展中的作用及其分子机制。LINC00520是一种新的黑色素瘤癌基因,可能成为黑色素瘤患者的生存生物标志物或治疗靶点。
BackgroundLong intergenic non-protein coding RNA 520 (LINC00520), a novel identified lncRNA, has been shown to modulate the malignant phenotype of tumor cells in some malignant tumors. However, the exact role and molecular mechanism of LINC00520 in malignant melanoma has not been studied.MethodsThe expression of LINC00520 in melanoma tissues were detected by using RNA-seq analysis and qRT-PCR. Melanoma cases from the public databases (The Cancer Genome Atlas (TCGA), GEO#GSE15605, GEO#GSE34460 and GEO#GSE24996) were included in this study. CCK-8 assay, EdU assay, transwell and scratch wound assay were used to explore the role of LINC00520 in melanoma cells. Luciferase reporter assays, MS2-RIP, RNA pull-down and RNA-ChIP assay were used to demonstrate the molecular biological mechanism of LINC00520 in melanoma.ResultsWe found that LICN00520 was found to be overexpressed in melanoma tissue. High expression of LICN00520 is a risk factor for the prognosis of melanoma patients. LINC00520 promotes the proliferation, invasion and migration of melanoma cells. LICN00520 exerted its oncogenic role by competitive binding miR-125b-5p to promote Eukaryotic initiation factor 5A2 (EIF5A2) expression. We also showed that LICN00520 promotes the growth and metastasis of melanoma in vivo through regulating miR-125b-5p/EIF5A2 axis.ConclusionsAll results elucidated the role and molecular mechanism of LINC00520 in the malignant development of melanoma. LINC00520, a new oncogene in melanoma, maybe serve as a survival biomarkers or therapeutic target for melanoma patients.