Premium
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
Author(s) -
Liu Tingwei,
Liu Fan,
Kang Jian
Publication year - 2020
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2306
Subject(s) - endoplasmic reticulum , unfolded protein response , chop , downregulation and upregulation , transfection , microbiology and biotechnology , apoptosis , medicine , cancer research , chemistry , biology , biochemistry , gene
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.