Suppression of microRNA-141 suppressed p53 to protect against neural apoptosis in epilepsy by SIRT1 expression

J Cell Biochem. 2019 Jun;120(6):9409-9420. doi: 10.1002/jcb.28216. Epub 2018 Dec 12.

Abstract

We investigated that microRNA (miRNA)-141 protects against epilepsy-induced apoptosis and its reaction mechanism. The serum expression of miRNA-141 in epilepsy model mice and control volunteer was measured by quantitative reverse-transcription polymerase chain reaction. We found that miRNA-141 serum expression was upregulated in patients with epilepsy. Overexpression of miRNA-141 induced nerve cell apoptosis, suppressed proliferation, promoted caspase-3/9, Bax and p53 protein expression, and reduced silent information regulator 1 (SIRT1) protein expression in vitro model. In addition, the downexpression miRNA-141 using si-miRNA-141 reduced nerve cell apoptosis and increased proliferation, suppressed caspase-3/9, Bax and p53 protein expression, induced SIRT1 protein expression. SIRT1 inhibitor (nicotinamide) decreased SIRT1, reduced the effects of miRNA-141 on nerve cell apoptosis in vitro model of epilepsy through SIRT1/p53. SIRT1 agonist also reduced the effects of miRNA-141 overexpression on nerve cell apoptosis in vitro model of epilepsy through SIRT1/p53. Our preliminary findings indicate that anti-miRNA-141 protects against epilepsy-induced apoptosis via SIRT1/p53 expression.

Keywords: SIRT1; apoptosis; epilepsy; microRNA-141; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Disease Models, Animal
  • Epilepsy / blood
  • Epilepsy / genetics*
  • Epilepsy / pathology
  • Epilepsy / therapy
  • Gene Expression Regulation / genetics
  • Humans
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Neurons / metabolism
  • Neurons / pathology
  • Protective Agents / pharmacology
  • Signal Transduction / genetics
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / blood
  • Sirtuin 1 / genetics*
  • Tumor Suppressor Protein p53 / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / blood
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • MicroRNAs
  • Mirn141 microRNA, mouse
  • Protective Agents
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • Sirt1 protein, mouse
  • Sirtuin 1