MiRNA-1976 Regulates the Apoptosis of Dopaminergic Neurons by Targeting the PINK1 Gene

J Integr Neurosci. 2023 Feb 22;22(2):45. doi: 10.31083/j.jin2202045.

Abstract

Introduction: Parkinson's disease (PD), which is a neurodegenerative disease, requires urgently needed biomarkers to explore its mechanism. We screened for differences in the expression of microRNAs (miRNAs) and identified miR-1976 as a possible biomarker.

Methods: Twenty-three patients and 30 controls were included in this study. Dopaminergic neurons from C57/BL mice were cultured. The miRNA expression profiles were analyzed using an miRNA microarray. MiR-1976 was identified as an miRNA that was differentially expressed between PD patients and age-matched controls. Lentiviral vectors were constructed, then apoptosis in dopaminergic neurons was analyzed using MTS (multicellular tumor spheroids) and flow cytometry. Transfection of miR-1976 mimics into MES23.5 cells was performed, and target genes and biological effects were analyzed.

Results: Overexpression of miR-1976 increased apoptosis and mitochondrial damage in dopaminergic neurons. PINK1 (PINK1-induced kinase 1) was the most common target protein of miR-1976, and silencing of PINK1 caused mitochondrial damage and increased apoptosis of MES23.5 cells.

Conclusions: MiR-1976 is a newly discovered miRNA that exhibits a high degree of differential expression with respect to the apoptosis of dopaminergic neurons. Given these results, increased expression of miR-1976 may increase the risk of PD by targeting PINK1 and may therefore be a useful biomarker for PD.

Keywords: PINK1; Parkinson's disease; apoptosis; biomarker; dopaminergic neuron; miR-1976; target protein.

MeSH terms

  • Animals
  • Apoptosis
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neurodegenerative Diseases* / metabolism
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Protein Kinases* / genetics
  • Protein Kinases* / metabolism

Substances

  • MicroRNAs
  • Protein Kinases
  • PTEN-induced putative kinase