MicroRNA-300: A Transcellular Mediator in Exosome Regulates Melanoma Progression
MicroRNA-300: A Transcellular Mediator in Exosome Regulates Melanoma Progression
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DOI：
10.3389/fonc.2019.01005
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发表时间：
2019-10-15
影响因子：
4.7
通讯作者：
Zhong, Li
中科院分区：
文献类型：
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作者：
Chen, Long;Karisma, Vega Windy;Zhong, Li
黑色素瘤是一种常见且死亡率高的皮肤癌。紫外线 (UV) 引起的氧化应激和 DNA 损伤是黑色素瘤形成的主要原因。但具体的分子机制仍不清楚。在这项研究中，通过分析测序数据集筛选了 218 个对紫外线反应失调的基因和 104 个失调的 miRNA。其中，29个上调的miRNA和28个下调的miRNA参与黑色素瘤通路。 GADD45B作为黑色素瘤通路中唯一的差异基因，严重影响黑色素瘤患者的预后。 MiR-300 是唯一调节 GADD45B 的差异表达 miRNA。此外，与正常黑色素细胞相比，miR-300在黑色素瘤细胞（log FC = -1.63）和外泌体（log FC = -1.34）中显着下调。在预测调节 miR-300 的转录因子中，MYC、PPARG 和 ZIC2 在黑色素瘤细胞中显着上调，TP53、JUN、JUNB、FOS 和 FOSB 与 GADD45B 相互作用。我们试图通过构建TF-mRNA-miRNA轴来揭示黑色素瘤的发病机制并筛选新的生物标志物，为进一步的研究提供视图。
Melanoma is a common and high-mortality skin cancer. Oxidative stress and DNA damage caused by ultraviolet light (UV) are major causative factors of melanoma formation. However, the specific molecular mechanism is still unclear. In this study, 218 dysregulated genes and 104 dysregulated miRNAs in response to UV were screened by analyzing sequencing datasets. Among them, 29 up-regulated miRNAs and 28 down-regulated miRNAs were involved in the melanoma pathway. As the only differential gene in the melanoma pathway, GADD45B severely affects the prognosis of melanoma patients. MiR-300 is the only differentially expressed miRNA that regulates GADD45B. In addition, compared to normal melanocytes, miR-300 was significantly down-regulated in melanoma cells (log FC = -1.63) and exosomes (log FC = -1.34). Among the transcription factors predicted to regulate miR-300, MYC, PPARG, and ZIC2 were significantly up-regulated in melanoma cells, and TP53, JUN, JUNB, FOS, and FOSB interacted with GADD45B. We attempted to reveal the pathogenesis of melanoma and screen new biomarkers by constructing a TF-mRNA-miRNA axis in turn to provide a view for further research.