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

doi:10.3892/mmr.2020.11601

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

Authors:
- Weize Yang
- Xiaomin Luo
- Yu Liu
- Jun Xiong
- Hongxia Xia
- Yafeng Liu
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Affiliations: Department of Emergency, The Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: October 14, 2020 https://doi.org/10.3892/mmr.2020.11601
Pages: 5095-5104
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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