LncRNA H19 Attenuates Apoptosis in MPTP-Induced Parkinson's Disease Through Regulating miR-585-3p/PIK3R3

Neurochem Res. 2020 Jul;45(7):1700-1710. doi: 10.1007/s11064-020-03035-w. Epub 2020 Apr 30.

Abstract

Parkinson's disease (PD) is a prevalent age-related neurodegenerative disease which is modulated by various molecules, including long non-coding RNAs (lncRNAs). LncRNA H19 has been shown to be associated with PD progression, but the mechanism is still unclear. This research aims to investigate the role of H19 in PD development and the detailed mechanisms. Our results showed that H19 was down-regulated in brain tissue of MPTP-induced PD mice (in vivo) and in MPP+ treated human neuroblastoma cells. miR-585-3p was verified to be a target of lncRNA H19 and was negatively regulated by H19. In addition, H19 could increase the expression of PIK3R3 through miR-585-3p. In vitro results indicated that H19 inhibited the apoptosis of MPP+ treated neuroblastoma cells by regulating of miR-585-3p. Moreover, in PD model mice, overexpression of H19 attenuated MPTP-induced neuronal apoptosis. In summary, our present research demonstrated that LncRNA H19 could attenuate neurons apoptosis in MPTP-induced PD mice as well as MPP+ treated neuroblastoma cells through regulating miR-585-3p/PIK3R3. The results may provide a potential theoretical experimental data for the clinical treatment of PD through targeting lncRNAs or miRNAs.

Keywords: LncRNA H19; PIK3R3; Parkinson's disease; miR-585-3p.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Line, Tumor
  • HEK293 Cells
  • Humans
  • MPTP Poisoning / chemically induced
  • MPTP Poisoning / metabolism*
  • MPTP Poisoning / prevention & control
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / biosynthesis*
  • RNA, Long Noncoding / biosynthesis*

Substances

  • H19 long non-coding RNA
  • MIRN585 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • pik3r3 protein, mouse