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微小 RNA-378 通过抑制 Wnt/β-连环蛋白通路中的 FOXN3 表达来调节黑色素瘤的上皮-间充质转化和转移。

MicroRNA-378 regulates epithelial-mesenchymal transition and metastasis of melanoma by inhibiting FOXN3 expression through the Wnt/β-catenin pathway.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, P. R. China.

Department of Dermatology, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi, 716000, P. R. China.

出版信息

Cell Biol Int. 2019 Oct;43(10):1113-1124. doi: 10.1002/cbin.11027. Epub 2019 Jul 23.

DOI:10.1002/cbin.11027
PMID:29972255
Abstract

MicroRNAs (miRNAs) participate in the development and progression of melanoma. However, while dysregulation of microRNA-378 (miR-378) has been seen in various cancer types, its clinical importance and function in melanoma are poorly elucidated. In this work, miR-378 expression in melanoma and in adjacent non-cancerous tissue was evaluated with a quantitative real-time polymerase chain reaction. A series of assays (wound healing, Transwell, and nude mouse subcutaneous tumor model) were used to investigate the implications of abnormal miR-378 regulation on melanoma cell migration and invasion in vitro, and on tumorigenicity in vivo. Prediction and conformation of the miR-378 target gene was undertaken using bioinformatic analysis and luciferase reporter system. Expression of miR-378 was often increased in melanoma, and shown to potentiate its migration, invasion, and tumorigenicity. miR-378 acted, at least partially, through inhibition of the potential target FOXN3 and via Wnt/β-catenin pathway activation. The findings indicate that miR-378 triggers melanoma development and progression. This miRNA could be a novel diagnostic and prognostic biological marker and provide utility for targeted treatment of melanoma.

摘要

微小 RNA(miRNA)参与黑色素瘤的发生和发展。然而,尽管 miRNA-378(miR-378)在各种癌症类型中存在失调,但它在黑色素瘤中的临床意义和功能仍未得到充分阐明。在这项工作中,通过实时定量聚合酶链反应评估了黑色素瘤和相邻非癌组织中的 miR-378 表达。一系列测定(划痕愈合、Transwell 和裸鼠皮下肿瘤模型)用于研究异常 miR-378 调节对黑色素瘤细胞体外迁移和侵袭以及体内致瘤性的影响。使用生物信息学分析和荧光素酶报告系统进行 miR-378 靶基因的预测和验证。miR-378 的表达在黑色素瘤中常常增加,并被证明增强其迁移、侵袭和致瘤性。miR-378 通过抑制潜在靶基因 FOXN3 并通过 Wnt/β-catenin 途径激活发挥作用。研究结果表明,miR-378 引发黑色素瘤的发生和发展。这种 miRNA 可以作为一种新的诊断和预后生物标志物,并为黑色素瘤的靶向治疗提供实用价值。

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