LncRNA DANCR improves the dysfunction of the intestinal barrier and alleviates epithelial injury by targeting the miR-1306-5p/PLK1 axis in sepsis

Cell Biol Int. 2021 Sep;45(9):1935-1944. doi: 10.1002/cbin.11633. Epub 2021 Jun 15.

Abstract

Intestinal barrier dysfunction often occurs in various acute or chronic pathological conditions and has been identified as an important clinical problem. Herein, we explored the biological role and molecular mechanism of Polo-like kinase 1 (PLK1) and differentiation antagonizing non-protein coding RNA (DANCR) in intestinal barrier dysfunction caused by sepsis. RT-qPCR analysis was used to examine PLK1, miR-1306-5p, and DANCR expression in NCM460 cells after LPS treatment. TUNEL assay and Western blot analysis were performed to explore PLK1 function in cell apoptosis and intestinal barrier in vitro. Hematoxylin and eosin staining, Western blot analysis, and TUNEL assay were used to investigate DANCR function in the intestinal barrier and cell apoptosis in vivo. The interaction between miR-1306-5p and PLK1 (or DANCR) was validated by luciferase reporter assay. As a result, PLK1 overexpression decreased cell apoptosis and promoted intestinal barrier function. Moreover, DANCR was validated as a sponge of miR-1306-5p to target PLK1. In addition, we found that DANCR overexpression decreased intestinal mucosal permeability and colon mucosa epithelial cell apoptosis in vivo. Conclusively, DANCR improved intestinal barrier dysfunction and alleviated epithelial injury by targeting the miR-1306-5p/PLK1 axis in sepsis.

Keywords: DANCR; PLK1; intestinal barrier dysfunction; miR-1306-5p.

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Colon* / metabolism
  • Colon* / pathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Long Noncoding / physiology*
  • Sepsis / metabolism*

Substances

  • Cell Cycle Proteins
  • DANCR long noncoding RNA, human
  • MIRN1306 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Long Noncoding
  • Protein Serine-Threonine Kinases