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LncRNA MIAT Promotes Inflammation and Oxidative Stress in Sepsis-Induced Cardiac Injury by Targeting miR-330-5p/TRAF6/NF-κB Axis

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Abstract

Sepsis is a whole-body inflammation and main cause of death in intensive care units worldwide. We aimed to investigate the roles of lncRNA MIAT and miR-330-5p in modulating inflammatory responses and oxidative stress in lipopolysachariden (LPS)-induced septic cardiomyopathy. Serum and heart tissue were collected from in vivo septic mice model, ELISA and qRT-PCR were used to measure the expression of pro-inflammation cytokines, MIAT and miR-330-5p, respectively. The knockdown of MIAT and overexpression of miR-330-5p were conducted to assess their effects on regulating inflammation response and intracellular oxidative stress in LPS-stimulated HL-1 cells. The reactive oxygen (ROS) level, mitochondrial membrane potential (MMP), GSH/GSSH ratio, and lipid peroxidation assessment (MDA) were used to evaluate the intracellular oxidative stress. Dual-luciferase reporter assay was performed to identify the association between MIAT and miR-330-5p, TRAF6 and miR-330-5p, respectively. In septic mice, the expression of MIAT and pro-inflammation cytokines was elevated while the expression of miR-330-5p decreased. Knockdown of MIAT or overexpression of miR-330-5p restrained inflammation and oxidative stress induced by LPS in vitro; MIAT directly targeted miR-330-5p to regulate NF-κB signaling, and miR-330-5p targeted against TRAF6 to suppress the activation of NF-κB signaling. We determined that lncRNA MIAT directly binds to miR-330-5p to activate TRAF6/NF-κB signaling axis and further promotes inflammation response as well as oxidative stress in LPS-induced septic cardiomyopathy. This finding suggests the potential therapeutic role of lncRNA MIAT and miR-330-5p in LPS-induced myocardial injury.

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Funding

The study was supported by Project of Beijing Medical Health Public Welfare Foundation (Grant No. B185040).

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Authors and Affiliations

  1. Department of Emergency, Shanghai University of Medicine & Health Sciences Affiliated Shanghai Sixth People’s Hospital East, No. 222, West Three Ring Road Around Lake, Pudong, 201306, Shanghai, People’s Republic of China

    Peng-Cheng Xing, Peng An, Guo-Yong Hu, Dong-Lian Wang & Min-Jie Zhou

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  1. Peng-Cheng Xing
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  2. Peng An
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  3. Guo-Yong Hu
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  4. Dong-Lian Wang
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Correspondence to Min-Jie Zhou.

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The authors of this study declared no conflict of interests.

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All animal experiments were approved by the Institutional Animal Care and Use Committee of the Shanghai Sixth People’s Hospital East.

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Xing, PC., An, P., Hu, GY. et al. LncRNA MIAT Promotes Inflammation and Oxidative Stress in Sepsis-Induced Cardiac Injury by Targeting miR-330-5p/TRAF6/NF-κB Axis. Biochem Genet 58, 783–800 (2020). https://doi.org/10.1007/s10528-020-09976-9

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  • DOI: https://doi.org/10.1007/s10528-020-09976-9

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