MicroRNA-421 suppresses the apoptosis and autophagy of hippocampal neurons in epilepsy mice model by inhibition of the TLR/MYD88 pathway

J Cell Physiol. 2018 Sep;233(9):7022-7034. doi: 10.1002/jcp.26498. Epub 2018 Mar 25.

Abstract

Epilepsy is a group of neurological disorders characterized by epileptic seizures. In this study, we aim to explore the role of microRNA-421 (miR-421) in hippocampal neurons of epilepsy mice via the TLR/MYD88 pathway. Forty mice were randomly served as the normal and model (established as epilepsy model) groups. Hippocampal neurons were assigned into seven groups with different transfections. The RT-qPCR and western blotting were conducted to examine the expression of miR-421 TLR2, TLR4, MYD88, Bax, Bcl-2, p53, Beclin-1, and LC3II/LC3I. Cell proliferation and apoptosis were detected by MTT and flow cytometry.MYD88 is a target gene of miR-421. Model mice showed elevated expression of TLR2, TLR4, MYD88, Bax, p53, Beclin-1, and LC3II/LC3I but reduced expression of miR-421 and Bcl-2. In vitro experiments reveals that overexpression of miR-421 inhibited the TLR/MYD88 pathway. Besides, overexpressed miR-421 declined cell apoptosis but increased cell proliferation. It reveals that miR-421 targeting MYD88 could inhibit the apoptosis and autophagy of hippocampal neurons in epilepsy mice by down-regulating the TLR/MYD88 pathway.

Keywords: TLR/MYD88 pathway; apoptosis; autophagy; epilepsy; hippocampal neurons; microRNA-421.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis* / genetics
  • Autophagy* / genetics
  • Base Sequence
  • CA1 Region, Hippocampal / pathology
  • CA1 Region, Hippocampal / ultrastructure
  • Cell Cycle Checkpoints
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Epilepsy / genetics*
  • Epilepsy / pathology
  • Hippocampus / pathology*
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myeloid Differentiation Factor 88 / metabolism*
  • Neurons / metabolism
  • Neurons / pathology*
  • RNA, Small Interfering / metabolism
  • S Phase
  • Signal Transduction
  • Toll-Like Receptors / metabolism*

Substances

  • MIRN421 microRNA, mouse
  • MicroRNAs
  • Myeloid Differentiation Factor 88
  • RNA, Small Interfering
  • Toll-Like Receptors