Silencing long non-coding RNA SNHG3 repairs the dysfunction of pulmonary microvascular endothelial barrier by regulating miR-186-5p/Wnt axis

Biochem Biophys Res Commun. 2023 Jan 8:639:36-45. doi: 10.1016/j.bbrc.2022.11.067. Epub 2022 Nov 24.

Abstract

Barrier permeability changes of human pulmonary microvascular endothelial cells (HPMVECs) are important in sepsis-related acute lung injury (ALI) pathogenesis. Long non-coding small nucleolar RNA host gene 3 (SNHG3) mediates the cell-biological phenotype of lung cancer cells and affects the progression of lung cancer, but its role in regulating functions of lung non-malignant cells is still rarely reported. Therefore, we evaluated the regulatory effect of SNHG3 on the function of PMVECs in sepsis-related ALI. Small interference RNA (siRNA)-mediated deletion of SNHG3 promoted the proliferation of PMVECs, reduced apoptosis and barrier permeability, and increased the expression of tight junction proteins claudin-5 and ZO-1. Knockdown of SNHG3 increased the miR-186-5p expression, while overexpression of SNHG3 upregulated the level of wnt5a. Through a dual luciferase reporter assay, we confirmed the binding between SNHG3 and miR-186-5p, miR-186-5p and wnt5a. We further found that knockout of miR-186-5p could inhibit cell proliferation, increase apoptosis and barrier permeability, and down-regulate claudin-5 and ZO-1. Importantly, silencing miR-186-5p and activating Wnt signal pathway could eliminate the barrier repair effect caused by down-regulation of SNHG3. To sum up, our results suggested that knockdown of long non-coding RNA SNHG3 repaired the dysfunction of pulmonary microvascular endothelial barrier through the miR-186-5p/Wnt axis.

Keywords: Acute lung injury; Endothelial barrier; SNHG3; Tight junction; Wnt; miR-186-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury* / etiology
  • Cell Proliferation / genetics
  • Claudin-5 / genetics
  • Endothelial Cells / metabolism
  • Humans
  • Lung / metabolism
  • Lung Neoplasms*
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Sepsis* / complications
  • Wnt Proteins / metabolism

Substances

  • Claudin-5
  • MicroRNAs
  • MIRN186 microRNA, human
  • RNA, Long Noncoding
  • Wnt Proteins