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

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

Yanli Wu  1 Mei Li  2 Jijia Bai  3 Xigang Ma  4

Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China; Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China.
  • 2 Department of Critical Care Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China.
  • 3 Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China.
  • 4 Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, PR China. Electronic address: nyfyicu@163.com.

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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.

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