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MIR3142HG promotes lipopolysaccharide-induced acute lung injury by regulating miR-450b-5p/HMGB1 axis

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Abstract

The present study aimed to evaluate the potential roles of MIR3142HG, a novel long non-coding RNA (lncRNA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was simulated by the treatment of LPS in human pulmonary microvascular endothelial cells (HPMECs). The expression of MIR3142HG, miR-450b-5p and high-mobility group box 1 (HMGB1) was determined by real-time PCR and western blotting. Functional analysis was performed through the assessment of cell viability, apoptosis and the production of proinflammatory cytokines. The interactions among MIR3142HG, miR-450b-5p and HMGB1 were analyzed by bioinformatics methods, dual-luciferase reporter and RNA pull-down assays. Using gain- and loss-of-function approaches, the in vitro functions of MIR3142HG and miR-450b-5p were subsequently assessed. MIR3142HG expression was upregulated, while miR-450b-5p was decreased in LPS-treated HPMECs. MIR3142HG knockdown protected against ALI induced by LPS through alleviating the apoptosis and inflammation of HPMECs. MIR3142HG impaired miR-450b-5p-mediated inhibition of HMGB1. Besides, the effects of MIR3142HG silencing could be alleviated by miR-4262 inhibition or HMGB1 overexpression. MIR3142HG mediated LPS-induced injury of HPMECs by targeting miR-450b-5p/HMGB1, suggesting that MIR3142HG might serve as a therapeutic potential for the treatment of ALI.

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Funding

This work was supported by the Biomedical and Engineering (Science) Interdisciplinary Study Fund of Shanghai Jiaotong University (YG2019QNA04 to Xiaolei Gong), the National Nature Science Foundation of China (81970439 to Jinlong Liu), Shanghai International Science and Technology Cooperation Projects (18410721400 to Jinlong Liu), and Fund of Shanghai Science and Technology Committee (17441903300 to Jinlong Liu; 17DZ2253100 to Jinfen Liu).

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, No.1678 Dongfang Road, Pudong New Area, Shanghai, 200127, China

    Xiaolei Gong, Limin Zhu, Jinlong Liu, Chunxiang Li, Zhuoming Xu, Jinfen Liu & Haibo Zhang

  2. Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Jinlong Liu

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  1. Xiaolei Gong
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Contributions

XLG, LMZ and JLL conceived and designed the experiments, CXL and ZMX analyzed and interpreted the results of the experiments, JFL and HBZ performed the experiments; all authors have read and approved the manuscript.

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Correspondence to Limin Zhu.

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11010_2021_4209_MOESM1_ESM.tif

MiR-450b-5p/HMGB1 acts on LPS-treated HPMECs through TLR4 and RAGEsignaling pathways. HPMECs were transfected with miR-450b-5p mimic or in combination with HMGB1before treatment with LPS (100ng/mL, 24h). (A) The protein levels of TLR4 andRAGE were detected by western blotting; (B) the mRNA expression of TLR4 andRAGE were detected by qRT‑ PCR. Data were shown as mean ± SD, n = 3. **P <0.01 (tif 1477 KB)

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Gong, X., Zhu, L., Liu, J. et al. MIR3142HG promotes lipopolysaccharide-induced acute lung injury by regulating miR-450b-5p/HMGB1 axis. Mol Cell Biochem 476, 4205–4215 (2021). https://doi.org/10.1007/s11010-021-04209-y

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