LncRNA FTX inhibits hippocampal neuron apoptosis by regulating miR-21-5p/SOX7 axis in a rat model of temporal lobe epilepsy

Biochem Biophys Res Commun. 2019 Apr 23;512(1):79-86. doi: 10.1016/j.bbrc.2019.03.019. Epub 2019 Mar 11.

Abstract

Emerging evidence has shown that long noncoding RNA (LncRNA) is involved in the development of epileptogenesis. However, the expression profile and the biological function of FTX in epilepsy remains unclear. This study aimed to provide functional evidence and elucidate the molecular mechanisms by which the FTX affects status epilepticus (SE) induced hippocampal apoptosis. SE rat model was introduced by intraperitoneal injection of lithium chloride and pilocarpine. Our results showed that FTX is notably reduced in the hippocampus. Moreover, the in vivo overexpression of FTX inhibited SE-induced hippocampus neuron apoptosis. Mechanically, we found that FTX negatively regulated miR-21-5p expression by targeting its 3'UTR to regulate neuron apoptosis. Upregulation of miR-21-5p attenuates anti-apoptosis property of FTX overexpression by regulating SOX7 expression in epileptiform hippocampal neurons. Collectively, our study for the first time demonstrated the anti-apoptosis ability of FTX during epileptogenesis and uncovered a novel FTX-mediated mechanism in SE-induced neural apoptosis by targeting miR-21-5p/SOX7 axis, which provides a new target in developing lncRNA-based strategies to reduce SE-induced hippocampal neuron apoptosis.

Keywords: Apoptosis; Epilepsy; SOX7; lncRNA FTX; miR-21-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Disease Models, Animal
  • Epilepsy, Temporal Lobe / genetics*
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / pathology
  • Gene Expression
  • Gene Knockdown Techniques
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • RNA, Long Noncoding / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • SOXF Transcription Factors / antagonists & inhibitors
  • SOXF Transcription Factors / genetics*
  • SOXF Transcription Factors / metabolism
  • Signal Transduction
  • Status Epilepticus / genetics
  • Status Epilepticus / metabolism
  • Status Epilepticus / pathology

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • SOXF Transcription Factors
  • mirn21 microRNA, rat