MicroRNA-345-5p regulates depression by targeting suppressor of cytokine signaling 1

Brain Behav. 2020 Sep;10(9):e01653. doi: 10.1002/brb3.1653. Epub 2020 Jul 30.

Abstract

Background/aims: MicroRNA(miR)-345-5p plays a key role in various cellular functions. However, the function of miR-345-5p in resistant depression (TRD) is unclear. The aim of this study was to evaluate the role and mechanism of miR-345-5p in the treatment of resistance depression (TRD).

Methods: RT-qPCR was used to detect the expression of miR-345-5p in BV-2 microglia. CCK-8 method and flow cytometry were used for cell viability and apoptosis of microglia. Target gene prediction and screening, and luciferase reporter assays were used to verify the downstream target gene of miR-345-5p. Western blot was used to analyze the protein expression of related proteins.

Results: miR-345-5p increased the cell viability of BV-2 microglia and the expression level of pro-inflammatory cytokines. In addition, the conditioned medium of microglia treated with miR-345-5p reduced the cell viability of HT22 hippocampal cells and caused S-phase arrest. The miR-345-5p-treated microglia induced apoptosis by regulating the expression levels of Bax, Bcl-2, pro-caspase-3, and cleaved caspase-3. Furthermore, SOCS1 was a direct target of miR-345-5p, and overexpression of SOCS1 was able to reverse the proapoptotic effect of miR-345-5p on activation of microglia on hippocampal neurons.

Conclusion: miR-345-5p induced inflammatory damage in hippocampal neurons by activating microglia. MiR-345-5p may be an effective target for TRD therapy.

Keywords: CDK6; SOCS1; apoptosis; depression; miR-345-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Survival
  • Cytokines / genetics
  • Depression*
  • MicroRNAs* / genetics

Substances

  • Cytokines
  • MicroRNAs