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LncRNA CASC9 attenuates lactate dehydrogenase-mediated oxidative stress and inflammation in spinal cord injury via sponging miR-383-5p

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Abstract

Long non-coding RNAs (lncRNAs) play important roles in various diseases, but the effect of lncRNA CASC9 on spinal cord injury (SCI) remains unclear. Therefore, the present study was conducted to explore the role of this lncRNA in SCI. SCI model was established by laminectomy in rats in vivo or induced by LPS in PC12 cells in vitro. Methylprednisolone (MP) was used for treatment in vivo. Spinal cord tissues were stained with H&E, and the oxidative stress- and inflammation-related factors were detected using their commercial kits. Cell apoptosis was determined using flow cytometry assay. Relative expression of corresponding genes was measured using qRT-PCR and western blotting. Luciferase reporter assay was used to verify binding site between CASC9 and miR-383-5p, as well as miR-383-5p and LDHA. The results showed that lncRNA CASC9 was downregulated and miR-383-5p was upregulated in SCI rats and LPS-induced PC12 cells. Severe histological injury and increased water content were also found in SCI rats. Increased levels of LDH, MDA, lactic acid, TNF-α, and IL-1β were found in SCI rats and LPS-induced PC12 cells. These changes could be reversed by MP treatment in vivo or overexpression of CASC9 in vitro. Besides, overexpression of CASC9 decreased cell apoptosis and protein expression of LDHA and increased protein expression of Nrf2 and HO-1 in LPS-induced PC12 cells. Furthermore, miR-383-5p was a direct target of CASC9 and was negatively regulated by CASC9. LDHA was a direct target of miR-383-5p and was negatively regulated by CASC9. In conclusion, lncRNA CASC9 exerted a protective role against oxidative stress, inflammation, and cell apoptosis in SCI, providing a novel therapeutic target or prognostic factor for SCI.

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All data generated or analyzed during this study are included in this published article.

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Authors and Affiliations

  1. Department of Neurosurgery, The First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China

    Congjin Guan

  2. Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321 zhongshan Road, Gulou District, Nanjing, 210008, Jiangsu, China

    Yi Wang

  3. Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, 210008, Jiangsu, China

    Yi Wang

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  1. Congjin Guan
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Yi Wang raised the concept. Yi Wang and Congjin Guan collected the data. Congjin Guan analyzed and interpreted the data. Yi Wang and Congjin Guan generated the manuscript.

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Correspondence to Yi Wang.

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All experiments were approved by the Animal Care and Use Committee at Nanjing Medical University.

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Guan, C., Wang, Y. LncRNA CASC9 attenuates lactate dehydrogenase-mediated oxidative stress and inflammation in spinal cord injury via sponging miR-383-5p. Inflammation 44, 923–933 (2021). https://doi.org/10.1007/s10753-020-01387-7

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