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NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage
Acute lung injury (ALI) is a devastating human malignancy characterized by excessively uncontrolled inflammation and lung endothelial dysfunction. Non-coding RNAs play essential roles in endothelial protections during the pathological processes of ALI. The precise functions and molecular mechanisms...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
De Gruyter
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989156/ https://www.ncbi.nlm.nih.gov/pubmed/35480402 http://dx.doi.org/10.1515/med-2022-0446 |
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author | Zhou, Yuhua Chen, Chunyan Li, Qingtian Sheng, Huiqiu Guo, Xiaokui Mao, Enqiang |
author_facet | Zhou, Yuhua Chen, Chunyan Li, Qingtian Sheng, Huiqiu Guo, Xiaokui Mao, Enqiang |
author_sort | Zhou, Yuhua |
collection | PubMed |
description | Acute lung injury (ALI) is a devastating human malignancy characterized by excessively uncontrolled inflammation and lung endothelial dysfunction. Non-coding RNAs play essential roles in endothelial protections during the pathological processes of ALI. The precise functions and molecular mechanisms of the lncRNA-NORAD-mediated endothelial protection remain obscure. This study reports NORAD was significantly induced in human pulmonary microvascular endothelial cells (HPMECs) under lipopolysaccharide (LPS) treatment. Silencing NORAD effectively protected HPMECs against the LPS-induced cell dysfunction. In addition, RNA pull-down and luciferase assay validated that NORAD sponged miR-30c-5p, which showed reverse functions of NORAD in the LPS-induced cell injury of HPMECs. Furthermore, the glucose metabolism of HPMECs was significantly elevated under LPS stimulation which promoted the glucose consumption and extracellular acidification rate (ECAR) of HPMECs. Inhibiting NORAD or overexpressing miR-30c-5p suppressed glucose metabolism in HPMECs, leading to protective effects on HPMECs under LPS stimulation. The glycolysis key enzyme, lactate dehydrogenase-A (LDHA), was subsequently identified as a direct target of miR-30c-5p. Finally, recovery of miR-30c-5p in NORAD-overexpressing HPMECs effectively overrode the NORAD-promoted glycolysis and impaired endothelial dysfunction under LPS stimulation by targeting LDHA. Summarily, we demonstrated a NORAD-miR-30c-5p-LDHA-glycolysis axis in the LPS-induced HPMECs dysfunction in vitro and in vivo, contributing to the development of anti-ALI therapeutic approaches. |
format | Online Article Text |
id | pubmed-8989156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | De Gruyter |
record_format | MEDLINE/PubMed |
spelling | pubmed-89891562022-04-26 NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage Zhou, Yuhua Chen, Chunyan Li, Qingtian Sheng, Huiqiu Guo, Xiaokui Mao, Enqiang Open Med (Wars) Research Article Acute lung injury (ALI) is a devastating human malignancy characterized by excessively uncontrolled inflammation and lung endothelial dysfunction. Non-coding RNAs play essential roles in endothelial protections during the pathological processes of ALI. The precise functions and molecular mechanisms of the lncRNA-NORAD-mediated endothelial protection remain obscure. This study reports NORAD was significantly induced in human pulmonary microvascular endothelial cells (HPMECs) under lipopolysaccharide (LPS) treatment. Silencing NORAD effectively protected HPMECs against the LPS-induced cell dysfunction. In addition, RNA pull-down and luciferase assay validated that NORAD sponged miR-30c-5p, which showed reverse functions of NORAD in the LPS-induced cell injury of HPMECs. Furthermore, the glucose metabolism of HPMECs was significantly elevated under LPS stimulation which promoted the glucose consumption and extracellular acidification rate (ECAR) of HPMECs. Inhibiting NORAD or overexpressing miR-30c-5p suppressed glucose metabolism in HPMECs, leading to protective effects on HPMECs under LPS stimulation. The glycolysis key enzyme, lactate dehydrogenase-A (LDHA), was subsequently identified as a direct target of miR-30c-5p. Finally, recovery of miR-30c-5p in NORAD-overexpressing HPMECs effectively overrode the NORAD-promoted glycolysis and impaired endothelial dysfunction under LPS stimulation by targeting LDHA. Summarily, we demonstrated a NORAD-miR-30c-5p-LDHA-glycolysis axis in the LPS-induced HPMECs dysfunction in vitro and in vivo, contributing to the development of anti-ALI therapeutic approaches. De Gruyter 2022-04-06 /pmc/articles/PMC8989156/ /pubmed/35480402 http://dx.doi.org/10.1515/med-2022-0446 Text en © 2022 Yuhua Zhou et al., published by De Gruyter https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. |
spellingShingle | Research Article Zhou, Yuhua Chen, Chunyan Li, Qingtian Sheng, Huiqiu Guo, Xiaokui Mao, Enqiang NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage |
title | NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage |
title_full | NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage |
title_fullStr | NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage |
title_full_unstemmed | NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage |
title_short | NORAD modulates miR-30c-5p-LDHA to protect lung endothelial cells damage |
title_sort | norad modulates mir-30c-5p-ldha to protect lung endothelial cells damage |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989156/ https://www.ncbi.nlm.nih.gov/pubmed/35480402 http://dx.doi.org/10.1515/med-2022-0446 |
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