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CircRNA3616 knockdown attenuates inflammation and apoptosis in spinal cord injury by inhibiting TLR4/NF-κB activity via sponging miR-137

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Abstract

Purpose

The present work focused on exploring the role of circRNA3616 in neuronal inflammation and apoptosis in spinal cord injury (SCI).

Methods

The SCI mouse model and circRNA3616 knockdown SCI mouse model were established. This work focused on assessing the mouse locomotor function using Basso Mouse Scale (BMS) and BMS subscore. Hematoxylin–eosin (HE) staining and Tunel staining were conducted, while myeloperoxidase (MPO) activity was also detected on spinal cord tissues. We also knocked down circRNA3616 expression in NSC-34 cells. Meanwhile, the SCI cell model was established by oxygen glucose deprivation (OGD) in NSC-34 cells. Moreover, we conducted dual-luciferase reporter gene assay. Flow cytometry (FCM) was conducted to detect SCI cell apoptosis, whereas cell counting kit-8 (CCK-8) assay was performed to analyze cell viability. This study also implemented enzyme-linked immunosorbent assay to detect inflammatory factors in spinal cord tissues, serum, and cells.

Results

CircRNA3616 knockdown reduced the damage, inflammatory response, apoptosis, and MPO activity in SCI mouse serum and spinal cord tissues. CircRNA3616 knockdown increased BMS and BMS subscore of SCI mice. CircRNA3616 up-regulated TLR4 expression by sponging miR-137. CircRNA3616 knockdown inhibited the TLR4, p-IkBα, p-p65/p65 protein expression, while promoting IkBα protein expression within SCI mouse spinal cord. TLR4 reversed circRNA3616 knockdown-induced inhibition on NF-κB pathway activity in SCI cells. CircRNA3616 knockdown attenuated neuronal cell inflammation and apoptosis via TLR4/NF-κB pathway after SCI.

Conclusion

CircRNA3616 silencing attenuates inflammation and apoptosis in SCI by inhibiting TLR4/NF-κB activity via sponging miR-137. CircRNA3616 is the possible anti-SCI therapeutic target.

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Data availability

Obtained in connection with the corresponding author.

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Acknowledgements

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Authors and Affiliations

  1. Department of Orthopedics, The Third Affiliated Hospital, Soochow University, No.185 Juqian Street, Changzhou, 213003, Jiangsu, China

    Li Wang, Zhiwen Song, Hongjun Zou, Haining Chen & Yong Hu

  2. Department of Orthopedics, The Third People’s Hospital of Yancheng City, Yancheng, 224001, Jiangsu, China

    Li Wang

  3. Department of Anesthesia, The Third People’s Hospital of Yancheng City, Yancheng, 224001, Jiangsu, China

    Xiangnan Li

  4. Department of Spine, The Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China

    Jinbo Liu

Authors
  1. Li Wang
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  2. Zhiwen Song
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  3. Hongjun Zou
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  4. Haining Chen
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  5. Yong Hu
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  6. Xiangnan Li
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Contributions

LW: conception and design and analysis of data. LW, ZS, HZ, HC, YH, XL and JL performed the experiments. HZ, HC, YH, XL and JL: drafting the article. LW and ZS: revision of the article critically for important intellectual content.

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Correspondence to Jinbo Liu.

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Wang, L., Song, Z., Zou, H. et al. CircRNA3616 knockdown attenuates inflammation and apoptosis in spinal cord injury by inhibiting TLR4/NF-κB activity via sponging miR-137. Mol Cell Biochem 478, 329–341 (2023). https://doi.org/10.1007/s11010-022-04509-x

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  • DOI: https://doi.org/10.1007/s11010-022-04509-x

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