MiR-1b up-regulation inhibits rat neuron proliferation and regeneration yet promotes apoptosis via targeting KLF7

Folia Neuropathol. 2021;59(1):67-80. doi: 10.5114/fn.2021.105132.

Abstract

Introduction: MicroRNA (miRNA) is known to be involved in nerve injury. Our study aimed to identify the role and mechanism of miR-1b in rat neuron proliferation, regeneration and apoptosis.

Material and methods: Neurons were successfully separated and identified using a microscope and immunofluorescence staining of microtubule-associated protein 2 (MAP-2). The expressions of miR-1b and Krüppel-like factor 7 (KLF7) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Neuron viability and apoptosis were detected by MTT assay and flow cytometry, respectively. Neuron regeneration states were observed using a microscope and analysed by the ImageJ software. Expressions of C-caspase-3 and cell regeneration-related proteins (nerve growth factor [NGF], ciliary neurotrophic factor [CNTF] and brain-derived neurotrophic factor [BDNF]) were measured by Western blot. Target genes and potential binding sites of KLF7 and miR-1b were predicted by TargetScan 7.2 and confirmed by dual luciferase reporter assay.

Results: Neurons were identified as MAP-2-positive. Up-regulation of miR-1b reduced neuron viability and regenerative ability, promoted neuron apoptosis and C-caspase-3 expression, and down-regulated the expressions of cell regeneration-related proteins. KLF7 was the target gene of miR-1b. Overexpressed KLF7 rescued the effects of up-regulation of miR-1b on neuron viability, regeneration and apoptosis. Expressions of NGF, CNTF and BDNF were suppressed yet C-caspase-3 expression was up-regulated by miR-1b mimic, which was partially rescued by overexpressed KLF7.

Conclusions: Up-regulation of miR-1b promoted rat neuron proliferation and regeneration yet inhibited apoptosis via targeting KLF7.

Keywords: Krüppel-like factor 7; cell regeneration.; neuron; miR-1b.

MeSH terms

  • Animals
  • Apoptosis*
  • Brain-Derived Neurotrophic Factor
  • Caspase 3 / metabolism
  • Cell Culture Techniques
  • Cell Proliferation / genetics*
  • Cell Proliferation / physiology
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / metabolism*
  • Rats
  • Rats, Wistar

Substances

  • Brain-Derived Neurotrophic Factor
  • KLF7 protein, rat
  • Kruppel-Like Transcription Factors
  • MIRN1 microRNA, rat
  • MicroRNAs
  • Casp3 protein, rat
  • Caspase 3