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

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.

CircRNA circFADS2 is under-expressed in sepsis and protects lung cells from LPS-induced apoptosis by downregulating miR-133a

“…In the present study, the effect of LPS on HBEpCs was measured. The data from RT-qPCR, MTT assay, cell apoptosis assay, and Western blot suggested that LPS treatment reinforced apoptosis and inflammatory responses and inhibited viability of HBEpCs, which was in line with previous studies [ 22 ], thus indicating the successful establishment of a sepsis model in vitro .…”

Long Non-Coding RNAs as Biomarkers and Therapeutic Targets in Sepsis

“…HULC and urothelial carcinoma-associated 1 increased the expression of IL6, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 after LPS-induced inflammation in an endothelial cell model, thereby impairing vascular endothelial functions ( 126 ). In consistent with the previous study, HULC silencing could reverse the sepsis process stimulated by LPS by modulating miR-128-3p/Rac family small GTPase 1 axis in human umbilical vein endothelial cells (HUVECs) ( 69 ). Additionally, MALAT1 was significantly elevated in LPS-stimulated CMVECs, accompanied by the increase of permeability and apoptosis of CMVECs ( 46 ).…”

Human milk extracellular vesicle miRNA expression and associations with maternal characteristics in a population-based cohort from the Faroe Islands

“…Many of the miRNAs altered between 14 and 30 days have been found in previous studies to have roles related to mammary gland development. For instance, miR-128-3p was upregulated in the second week postpartum and is known to target RAC1 (Rac family small GTPase 1), the key GTPase in clearance of apoptotic cells during involution in mammary gland remodeling 69 , 70 . miR-27a-5p was downregulated in milk EVs.…”