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Long non-coding RNA NEAT1 promotes lipopolysaccharide-induced injury in human tubule epithelial cells by regulating miR-93-5p/TXNIP axis

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Abstract

Many long non-coding RNAs (lncRNAs) have been found to play crucial roles in sepsis-induced acute kidney injury (AKI), including lncRNA nuclear-enriched abundant transcript 1 (NEAT1). We aimed to further elucidate the functions and molecular mechanism of NEAT1 in sepsis-induced AKI. Sepsis-induced AKI cell model was established by treatment with lipopolysaccharide (LPS) in human tubule epithelial (HK2) cells. Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Western blot assay was performed to measure all protein levels. The concentrations of inflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression levels of inflammatory factors, NEAT1, microRNA-93-5p (miR-93-5p), and thioredoxin-interacting protein (TXNIP) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The oxidative stress factors were detected using corresponding kits. The interaction between miR-93-5p and NEAT1 or TXNIP was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. NEAT1 was upregulated in serum of sepsis patients and LPS-induced HK2 cells. NEAT1 silence alleviated LPS-induced HK2 cell injury by inhibiting apoptosis, inflammation and oxidative stress. Moreover, miR-93-5p was a direct target of NEAT1, and suppression of NEAT1 weakened LPS-induced injury by upregulating miR-93-5p in HK2 cells. Furthermore, TXNIP was a downstream target of miR-93-5p, and miR-93-5p attenuated LPS-induced HK2 cell injury by downregulating TXNIP. In addition, NEAT1 regulated TXNIP expression by acting as a sponge of miR-93-5p. NEAT1 might aggravate LPS-induced injury in HK2 cells by regulating miR-93-5p/TXNIP axis, providing a potential therapeutic strategy for sepsis-associated AKI.

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  1. Jing Yang and Lin Wu are co-first authors.

Authors and Affiliations

  1. Department of Emergency, Xijing Hospital, Xi’an, Shanxi, China

    Jing Yang, Lin Wu, Shanshou Liu, Xiaomin Hu & Qianmei Wang

  2. Department of Respiratory and Critical Care Medicine, The Fourth People’s Hospital of Shaanxi Province, No. 512, Xianning East Road, Xincheng District, Xi’an City, 710043, Shanxi Province, China

    Liying Fang

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Yang, J., Wu, L., Liu, S. et al. Long non-coding RNA NEAT1 promotes lipopolysaccharide-induced injury in human tubule epithelial cells by regulating miR-93-5p/TXNIP axis. Med Microbiol Immunol 210, 121–132 (2021). https://doi.org/10.1007/s00430-021-00705-6

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