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.

中文翻译：

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Let-7b-5p通过上调应激相关内质网蛋白1的表达参与急性肺栓塞内质网应激反应

内源性非编码微 RNA (miRNA) let-7b-5p 在急性肺栓塞 (PE) 患者的血液中高度表达。然而，let-7b-5p 参与急性 PE 的机制尚不清楚。为了解决这个问题，我们在体外和体内实验模型中研究了 let-7b-5p 在急性 PE 中的作用。结果表明，let-7b-5p在转录后水平上调应激相关内质网蛋白1（SERP1）的表达。SERP1 激活导致其伴侣蛋白 SEC61B 在响应内质网 (ER) 应激时发生调节。此外，我们的数据显示未折叠蛋白反应被触发，未折叠蛋白 GRP78、PERK、RNF121 和 CHOP 的激活通过 PERK-CHOP 途径发生，导致肺上皮细胞的炎症反应和凋亡。let-7b-5p 模拟物的体外表达促进了这些特征；相反，用 let-7b-5p 抑制剂转染会降低急性 PE 中 ER 应激的反应。因此，这项研究的结果提供了证据，即 let-7b-5p 通过上调 SERP1 表达促进 ER 应激反应期间的蛋白质加工，最终导致肺细胞的炎症反应和凋亡，在急性 PE 的发病机制中累积起关键作用。