Hsa-miR-346 plays a role in the development of sepsis by downregulating SMAD3 expression and is negatively regulated by lncRNA MALAT1

Mol Cell Probes. 2019 Oct:47:101444. doi: 10.1016/j.mcp.2019.101444. Epub 2019 Sep 5.

Abstract

Sepsis is a common complication in infection, trauma, and surgery. Severe sepsis has been identified as the leading cause of death in patients suffering from noncardiovascular ailments in intensive care units. In the current study, we used lipopolysaccharide (LPS) to stimulate the mouse macrophage cell line RAW264.7, and investigated the effects of the lncRNA MALAT1/hsa-miR-346/SMAD3 regulatory network on the progression of sepsis. We showed that MALAT1 inhibited RAW264.7 cell proliferation, while hsa-miR-346 promoted its proliferation. In this RAW264.7 cell model, MALAT1 inhibited hsa-miR-346 expression, and upregulated SMAD3 protein expression. The SMAD3 protein expression in RAW264.7 cells was significantly downregulated upon the overexpression of hsa-miR-346. These results suggest that the MALAT1/hsa-miR-346/SMAD3 regulatory network plays a key role in the development of sepsis, and may serve as a target for the treatment of sepsis.

Keywords: Hsa-miR-346; SMAD3; Sepsis; lncRNA MALAT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Animals
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Humans
  • Lipopolysaccharides / adverse effects
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • RAW 264.7 Cells
  • RNA, Long Noncoding / genetics*
  • Sepsis / genetics*
  • Sepsis / metabolism
  • Smad3 Protein / genetics*
  • Smad3 Protein / metabolism
  • Young Adult

Substances

  • 3' Untranslated Regions
  • Lipopolysaccharides
  • MALAT1 long non-coding RNA, human
  • MIRN346 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SMAD3 protein, human
  • Smad3 Protein