Neoplasma. 2018;65(1):89-96. doi: 10.4149/neo_2018_161128N594.
Recent studies have confirmed the existence of BDNF and tropomyosin-related kinase B (TrkB) in normal and cancerous urothelium. However, the corresponding mechanisms and upstream signal pathways of BDNF/TrkB have not been fully discovered. This study aimed to investigate the effects of miR-1-3p on bladder cancer (BC) by regulating BDNF-TrkB signal pathway. The expression of miR-1-3p and BDNF in BC tissues and cell lines were detected by Cancer Genome Atlas (TCGA) microarray analysis, RT-qPCR and western blot. Cell transfection was done using Lipofectamine 2000. Then cell viability, proliferation, migration and apoptosis were measured by MTT, colony formation assay, Transwell assay and flow cytometry, respectively. The relationship between miR-1-3p and BDNF was confirmed by luciferase reporter gene assay. MiR-1-3p was significantly down-regulated in BC tissues and cell lines, while BDNF was significantly up-regulated compared to normal samples. MiR-1-3p targeted BDNF and suppressed its expression. Transfections of miR-1-3p mimics and BDNF siRNAs can suppress BC cell proliferation, invasion and induce cell apoptosis. In addition, miR-1-3p can inhibit phosphorylation of the TrkB by regulating BDNF.In conclusion, MiR-1-3p has significant effects on viability, proliferation, invasion and apoptosis of BC cells by regulating BDNF-TrkB pathway.
最近的研究证实，BDNF 和原肌球蛋白相关激酶 B（TrkB）存在于正常和癌变的尿路上皮中。然而，BDNF/TrkB 的相应机制和上游信号通路尚未完全发现。本研究旨在通过调节 BDNF-TrkB 信号通路来研究 miR-1-3p 对膀胱癌（BC）的影响。通过癌症基因组图谱（TCGA）微阵列分析、RT-qPCR 和 Western blot 检测 BC 组织和细胞系中 miR-1-3p 和 BDNF 的表达。使用 Lipofectamine 2000 进行细胞转染。然后通过 MTT、集落形成实验、Transwell 实验和流式细胞术分别测量细胞活力、增殖、迁移和凋亡。通过荧光素酶报告基因实验证实了 miR-1-3p 与 BDNF 的关系。miR-1-3p 在 BC 组织和细胞系中明显下调，而与正常样本相比，BDNF 明显上调。miR-1-3p 靶向 BDNF 并抑制其表达。miR-1-3p 模拟物和 BDNF siRNAs 的转染可以抑制 BC 细胞增殖、侵袭并诱导细胞凋亡。此外，miR-1-3p 可以通过调节 BDNF 来抑制 TrkB 的磷酸化。总之，miR-1-3p 通过调节 BDNF-TrkB 通路对 BC 细胞的活力、增殖、侵袭和凋亡有显著影响。
