Mechanism of Snhg8/miR-384/Hoxa13/FAM3A axis regulating neuronal apoptosis in ischemic mice model

Cell Death Dis. 2019 Jun 5;10(6):441. doi: 10.1038/s41419-019-1631-0.


Long noncoding RNAs, a subgroup of noncoding RNAs, are implicated in ischemic brain injury. The expression levels of Snhg8, miR-384, Hoxa13, and FAM3A were measured in chronic cerebral ischemia-induced HT22 cells and hippocampal tissues. The role of the Snhg8/miR-384/Hoxa13/FAM3A axis was evaluated in chronic cerebral ischemia models in vivo and in vitro. In this study, we found that Snhg8 and Hoxa13 were downregulated, while miR-384 was upregulated in chronic cerebral ischemia-induced HT22 cells and hippocampal tissues. Overexpression of Snhg8 and Hoxa13, and silencing of miR-384, all inhibited chronic cerebral ischemia-induced apoptosis of HT22 cells. Moreover, Snhg8 bound to miR-384 in a sequence-dependent manner and there was a reciprocal repression between Snhg8 and miR-384. Besides, overexpression of miR-384 impaired Hoxa13 expression by targeting its 3'UTR and regulated chronic cerebral ischemia-induced neuronal apoptosis. Hoxa13 bound to the promoter of FAM3A and enhanced its promotor activity, which regulated chronic cerebral ischemia-induced neuronal apoptosis. Remarkably, the in vivo experiments demonstrated that Snhg8 overexpression combined with miR-384 knockdown led to an anti-apoptosis effect. These results reveal that the Snhg8/miR-384/Hoxa13/FAM3A axis plays a critical role in the regulation of chronic cerebral ischemia-induced neuronal apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis / genetics*
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Cell Line
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Hippocampus / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / metabolism*
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation


  • 3' Untranslated Regions
  • Cytokines
  • FAM3A protein, mouse
  • Homeodomain Proteins
  • MIRN384 microRNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding
  • homeobox protein HOXA13