MiR-122-5p Mitigates Inflammation, Reactive Oxygen Species and SH-SY5Y Apoptosis by Targeting CPEB1 After Spinal Cord Injury Via the PI3K/AKT Signaling Pathway

Neurochem Res. 2021 Apr;46(4):992-1005. doi: 10.1007/s11064-021-03232-1. Epub 2021 Feb 2.

Abstract

Spinal cord injury (SCI) is a threatening disease that lead to severe motor and sensory deficits. Previous research has revealed that miRNAs are involved in the pathogenesis of a variety of diseases. However, whether miR-122-5p was involved in SCI was rarely investigated. In our study, we intended to probe role of miR-122-5p in the regulation of inflammatory response, reactive oxygen species (ROS) and SH-SY5Y apoptosis. We found miR-122-5p was downregulated in SCI mouse model and LPS-induced SH-SY5Y cells. Moreover, miR-122-5p overexpression alleviated inflammatory response, ROS and SH-SY5Y apoptosis in SCI mice. In addition, miR-122-5p elevation also mitigated SCI in LPS-induced SH-SY5Y cells. Additionally, cytoplasmic polyadenylation element binding protein 1 (CPEB1) was verified to be a target of miR-122-5p. CPEB1 expression was upregulated in SCI mouse model and LPS-induced SH-SY5Y cells. CPEB1 expression was negatively related to miR-122-5p expression. Moreover, CPEB1 activated the PI3K/AKT signaling pathway in SH-SY5Y cells. Finally, CPEB1 elevation recovered the suppressive effect on inflammatory response, ROS and SH-SY5Y apoptosis in LPS-treated SH-SY5Y cells mediated by miR-122-5p upregulation and through the PI3K/AKT signaling pathway.

Keywords: CPEB1; PI3K/AKT signaling pathway; Spinal cord injury; miR-122-5p.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Humans
  • Inflammation / etiology
  • Inflammation / metabolism*
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / physiology
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / metabolism*
  • Transcription Factors / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • mRNA Cleavage and Polyadenylation Factors / metabolism*

Substances

  • CPEB1 protein, human
  • Lipopolysaccharides
  • MIRN122 microRNA, human
  • MicroRNAs
  • Reactive Oxygen Species
  • Transcription Factors
  • mRNA Cleavage and Polyadenylation Factors
  • Proto-Oncogene Proteins c-akt