Let‐7b‐5p is involved in the response of endoplasmic reticulum stress in acute pulmonary embolism through upregulating the expression of stress‐associated endoplasmic reticulum protein 1

The endogenous non‐coding microRNA (miRNA) let‐7b‐5p is highly expressed in the blood of patients with acute pulmonary embolism (PE). However, the mechanism underlying the involvement of let‐7b‐5p in acute PE remains unclear. To address this, we investigated the role of let‐7b‐5p in acute PE in both...

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Bibliographic Details
Published in:IUBMB life 2020-08, Vol.72 (8), p.1725-1736
Main Authors: Liu, Ting‐wei, Liu, Fan, Kang, Jian
Format: Article
Language:English
Subjects:
acute pulmonary embolism
Apoptosis
Embolism
Endoplasmic reticulum
endoplasmic reticulum stress
Epithelial cells
Inflammation
inositol‐requiring kinase‐I
let‐7b‐5p
MicroRNAs
miRNA
Protein folding
Proteins
Pulmonary embolisms
Stress response
stress‐associated endoplasmic reticulum protein 1 (SERP1)
Transcription activation
Transfection
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Summary:The endogenous non‐coding microRNA (miRNA) let‐7b‐5p is highly expressed in the blood of patients with acute pulmonary embolism (PE). However, the mechanism underlying the involvement of let‐7b‐5p in acute PE remains unclear. To address this, we investigated the role of let‐7b‐5p in acute PE in both in vitro and in vivo experimental models. The results showed that let‐7b‐5p upregulated the expression of stress‐associated endoplasmic reticulum protein 1 (SERP1) at the post‐transcriptional level. SERP1 activation leads to modulation of its chaperone protein SEC61B in the response of endoplasmic reticulum (ER) stress. Furthermore, our data show that the unfolded protein response was triggered and activation of unfolded proteins GRP78, PERK, RNF121, and CHOP occurred through the PERK‐CHOP pathway, resulting in an inflammatory response and apoptosis of lung epithelial cells. These characteristics were promoted by the in vitro expression of a let‐7b‐5p mimic; conversely, transfection with a let‐7b‐5p inhibitor decreased the response of ER stress in acute PE. The results from this study thus provide evidence that let‐7b‐5p promotes protein processing during ER stress response by upregulating SERP1 expression, ultimately resulting in an inflammatory response and apoptosis of lung cells, cumulatively playing a critical role in the pathogenesis of acute PE.
ISSN:1521-6543
1521-6551
DOI:10.1002/iub.2306