Identification of antisense lncRNAs targeting GSK3β as a regulator in major depressive disorder

Epigenomics. 2020 Oct;12(19):1725-1738. doi: 10.2217/epi-2019-0402. Epub 2020 Sep 8.

Abstract

Aim: To identify lncRNAs targeting GSK3β in MDD. Materials & methods: The levels of GSK3β and its three targeting lncRNAs (gsk3β antisense AS1, AS2 and AS3) were detected in 52 patients with major depressive disorder (MDD) before and after 8 weeks of escitalopram treatment. The functional study was evaluated using the silence of lncR-gsk3βAS2/3. The correlation between lncRNA-gsk3β and 89 MDD patients was analyzed. Human neuron progenitor cells were used to investigate the functional role of lncRNA-gsk3β in MDD. Results: All three lncRNAs were downregulated in MDD patients but upregulated after treatment. Inhibition of gsk3βAS2/3 reduced GSK3β expression and its phosphorylation levels in the neuron progenitor cells. Conclusion: Our findings suggest that lncRNA-gsk3βAS3 regulates GSK3β activity in MDD and has potential as a novel therapeutic target.

Keywords: GSK3β; antidepressant strategy; lncRNA; major depressive disorder; neuroplasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / enzymology
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Glycogen Synthase Kinase 3 beta / genetics*
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Middle Aged
  • Neural Stem Cells / enzymology
  • Neural Stem Cells / metabolism
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / metabolism*

Substances

  • RNA, Antisense
  • RNA, Long Noncoding
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta