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Potential role of lncRNA HULC/miR-128-3p/RAC1 axis in the inflammatory response during LPS-induced sepsis in HMEC-1 cells

Sepsis is a serious clinical condition characterized by systemic inflammation. The long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) was validated to partake in the development of sepsis. The present study aimed to investigate the potential mechanism of HULC in lipopolysaccharide...

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Autores principales: Yang, Weize, Luo, Xiaomin, Liu, Yu, Xiong, Jun, Xia, Hongxia, Liu, Yafeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646959/
https://www.ncbi.nlm.nih.gov/pubmed/33174038
http://dx.doi.org/10.3892/mmr.2020.11601
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author Yang, Weize
Luo, Xiaomin
Liu, Yu
Xiong, Jun
Xia, Hongxia
Liu, Yafeng
author_facet Yang, Weize
Luo, Xiaomin
Liu, Yu
Xiong, Jun
Xia, Hongxia
Liu, Yafeng
author_sort Yang, Weize
collection PubMed
description Sepsis is a serious clinical condition characterized by systemic inflammation. The long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) was validated to partake in the development of sepsis. The present study aimed to investigate the potential mechanism of HULC in lipopolysaccharide (LPS)-induced sepsis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis was employed to examine the expression of HULC, microRNA (miR)-128-3p, Rac family small GTPase 1 (RAC1) and pro-inflammatory factors [IL-6, TNF-α, intercellular adhesion molecule (ICAM1) and vascular cell adhesion molecule (VCAM1)] in the serum of patients with sepsis or LPS-induced human dermal microvascular endothelial cells (HMEC-1). Flow cytometry and western blot assays were performed to detect cell apoptosis. The targeted relationship among HULC, miR-128-3p and RAC1 was confirmed by a dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP) assay and RNA pull-down assay. HULC and RAC1 were found to be upregulated, and miR-128-3p was downregulated in the serum of patients with sepsis and LPS-stimulated HMEC-1 cells. LPS promoted apoptosis and inflammation, which were decreased by silencing of HULC. HULC targeted miR-128-3p and negatively regulated its expression. HULC knockdown protected HMEC-1 cells from LPS-induced injury by upregulating miR-128-3p. RAC1 was a target of miR-128-3p, and gain of RAC1 also relieved the silencing of HULC-mediated suppressive effects on apoptosis and inflammation in LPS-stimulated HMEC-1 cells. In conclusion, HULC knockdown partially reversed LPS-induced sepsis via the regulation of miR-128-3p/RAC1 axis.
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spelling pubmed-76469592020-11-13 Potential role of lncRNA HULC/miR-128-3p/RAC1 axis in the inflammatory response during LPS-induced sepsis in HMEC-1 cells Yang, Weize Luo, Xiaomin Liu, Yu Xiong, Jun Xia, Hongxia Liu, Yafeng Mol Med Rep Articles Sepsis is a serious clinical condition characterized by systemic inflammation. The long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) was validated to partake in the development of sepsis. The present study aimed to investigate the potential mechanism of HULC in lipopolysaccharide (LPS)-induced sepsis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis was employed to examine the expression of HULC, microRNA (miR)-128-3p, Rac family small GTPase 1 (RAC1) and pro-inflammatory factors [IL-6, TNF-α, intercellular adhesion molecule (ICAM1) and vascular cell adhesion molecule (VCAM1)] in the serum of patients with sepsis or LPS-induced human dermal microvascular endothelial cells (HMEC-1). Flow cytometry and western blot assays were performed to detect cell apoptosis. The targeted relationship among HULC, miR-128-3p and RAC1 was confirmed by a dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP) assay and RNA pull-down assay. HULC and RAC1 were found to be upregulated, and miR-128-3p was downregulated in the serum of patients with sepsis and LPS-stimulated HMEC-1 cells. LPS promoted apoptosis and inflammation, which were decreased by silencing of HULC. HULC targeted miR-128-3p and negatively regulated its expression. HULC knockdown protected HMEC-1 cells from LPS-induced injury by upregulating miR-128-3p. RAC1 was a target of miR-128-3p, and gain of RAC1 also relieved the silencing of HULC-mediated suppressive effects on apoptosis and inflammation in LPS-stimulated HMEC-1 cells. In conclusion, HULC knockdown partially reversed LPS-induced sepsis via the regulation of miR-128-3p/RAC1 axis. D.A. Spandidos 2020-12 2020-10-14 /pmc/articles/PMC7646959/ /pubmed/33174038 http://dx.doi.org/10.3892/mmr.2020.11601 Text en Copyright: © Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yang, Weize
Luo, Xiaomin
Liu, Yu
Xiong, Jun
Xia, Hongxia
Liu, Yafeng
Potential role of lncRNA HULC/miR-128-3p/RAC1 axis in the inflammatory response during LPS-induced sepsis in HMEC-1 cells
title Potential role of lncRNA HULC/miR-128-3p/RAC1 axis in the inflammatory response during LPS-induced sepsis in HMEC-1 cells
title_full Potential role of lncRNA HULC/miR-128-3p/RAC1 axis in the inflammatory response during LPS-induced sepsis in HMEC-1 cells
title_fullStr Potential role of lncRNA HULC/miR-128-3p/RAC1 axis in the inflammatory response during LPS-induced sepsis in HMEC-1 cells
title_full_unstemmed Potential role of lncRNA HULC/miR-128-3p/RAC1 axis in the inflammatory response during LPS-induced sepsis in HMEC-1 cells
title_short Potential role of lncRNA HULC/miR-128-3p/RAC1 axis in the inflammatory response during LPS-induced sepsis in HMEC-1 cells
title_sort potential role of lncrna hulc/mir-128-3p/rac1 axis in the inflammatory response during lps-induced sepsis in hmec-1 cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646959/
https://www.ncbi.nlm.nih.gov/pubmed/33174038
http://dx.doi.org/10.3892/mmr.2020.11601
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