MiR-1-3p inhibits cell proliferation and invasion by regulating BDNF-TrkB signaling pathway in bladder cancer

Neoplasma. 2018;65(1):89-96. doi: 10.4149/neo_2018_161128N594.

Abstract

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.

Keywords: BDNF; MiR-1-3p; TrkB bladder cancer..

MeSH terms

  • Apoptosis
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Glycoproteins / metabolism*
  • MicroRNAs / genetics*
  • Receptor, trkB / metabolism*
  • Signal Transduction*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Brain-Derived Neurotrophic Factor
  • MIRN1 microRNA, human
  • Membrane Glycoproteins
  • MicroRNAs
  • BDNF protein, human
  • Receptor, trkB
  • tropomyosin-related kinase-B, human