Effects of microRNA-129 and its target gene c-Fos on proliferation and apoptosis of hippocampal neurons in rats with epilepsy via the MAPK signaling pathway

J Cell Physiol. 2018 Sep;233(9):6632-6643. doi: 10.1002/jcp.26297. Epub 2018 Apr 11.

Abstract

This study aims to investigate the effect of microRNA-129 (miR-129) on proliferation and apoptosis of hippocampal neurons in epilepsy rats by targeting c-Fos via the MAPK signaling pathway. Thirty rats were equally classified into a model group (successfully established as chronic epilepsy models) and a normal group. Expression of miR-129, c-Fos, bax, and MAPK was detected by RT-qPCR and Western blotting. Hippocampal neurons were assigned into normal, blank, negative control (NC), miR-129 mimic, miR-129 inhibitor, siRNA-c-Fos, miR-129 inhibitor+siRNA-c-Fos groups. The targeting relationship between miR-129 and c-Fos was predicted and verified by bioinformatics websites and dual-luciferase reporter gene assay. Cell proliferation after transfection was measured by MTT assay, and cell cycle and apoptosis by flow cytometry. c-Fos is a potential target gene of miR-129. Compared with the normal group, the other six groups showed a decreased miR-129 expression; increased expression of expression of c-Fos, Bax, and MAPK; decreased proliferation; accelerated apoptosis; more cells arrested in the G1 phase; and fewer cells arrested in the S phase. Compared with the blank and NC groups, the miR-129 mimic group and the siRNA-c-Fos group showed decreased expression of c-Fos, Bax, and MAPK, increased cells proliferation, and decreased cell apoptosis, fewer cells arrested in the G1 phase and more cells arrested in the S phase. However, the miR-129 inhibitor groups showed reverse consequences. This study suggests that miR-129 could inhibit the occurrence and development of epilepsy by repressing c-Fos expression through inhibiting the MAPK signaling pathway.

Keywords: MAPK signaling pathway; apoptosis; c-Fos; epilepsy; hippocampal neurons; microRNA-129.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Epilepsy / genetics
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Hippocampus / pathology*
  • MAP Kinase Signaling System / genetics*
  • MicroRNAs / genetics*
  • Neurons / pathology*
  • Proto-Oncogene Proteins c-fos / genetics*
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / genetics

Substances

  • MIRN129 microRNA, rat
  • MicroRNAs
  • Proto-Oncogene Proteins c-fos
  • RNA, Small Interfering