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Overexpression of miR-378 Alleviates Chronic Sciatic Nerve Injury by Targeting EZH2

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Abstract

In numerous studies, microRNAs (miRNAs) have been authenticated to play vital roles in the pathophysiology of neuropathic pain and other neurological diseases. In our study, we focused on evaluating miR-378 and its potential effects in neuropathic pain development, as well as the underlying molecular mechanisms. Primarily, a chronic sciatic nerve injury (CCI) rat model was established. Next, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure the expression levels of miR-378 and EZH2 mRNA; the EZH2 protein expression levels were detected by western blot. A luciferase activity assay monitored the interaction of miR-378 and EZH2. Mechanical and thermal hyperalgesia was also performed to quantitate the effects of overexpression of miR-378 or EZH2 on the CCI rats. We found that miR-378 was down-regulated in the CCI rats, and the overexpression of miR-378 produced significant relief in their pain management. EZH2 was the downstream gene of miR-378 and was negatively regulated by miR-378. The up-regulation of EZH2 reduced the inhibitory effects of miR-378 on the development of neuropathic pain in the CCI rats. miR-378 acts as an inhibitor in the progression of neuropathic pain via targeting EZH2; the miR-378/EZH2 axis may be a novel target for the diagnosis and therapy of neuropathic pain in clinical treatment.

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Data Availability

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

Abbreviations

CCI:

Chronic sciatic nerve injury

qRT-PCR:

Reverse transcription-quantitative polymerase chain reaction

SNI:

Spared nerve injury

RPMI-1640:

Roswell Park memorial Institute

NC:

Negative control

PWT:

Paw withdrawal threshold

PWL:

Paw withdrawal latency

RIPA:

Radio immunoprecipitation assay

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gels

PVDF:

Poly vinylidene difluoride

SD:

Standard deviation

EZH2:

Enhancer of zeste homolog 2

PRC2:

Polycomb repressive complex 2

H3K27me3:

Mythelation of lysine 27 on histone 3

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Acknowledgements

None.

Funding

This work was supported by The National Natural Science Foundation of China (No.81772044).

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Authors and Affiliations

  1. Department of Anesthesiology, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China

    Pengfei Gao & Xianlong Zhang

  2. Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei Province, Wuhan, China

    Xin Zeng, Lin Zhang, Long Wang & Fang Zhou

  3. Department of Anesthesiology, Huai’an Second People’s Hospital and The Affiliated Huai’an Hospital of Xuzhou Medical University, 66 Huaihai South Road, Huai’an, Jiangsu, China

    Lu-Lu Shen

  4. Department of Anesthesiology, Huai’an Hospital of Traditional Chinese Medicine, 3 Heping Road, Huai’an, Jiangsu, China

    Ya-Yun Hou

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  1. Pengfei Gao
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  3. Lin Zhang
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  4. Long Wang
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Correspondence to Xianlong Zhang.

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This study was approved by the ethics committee at Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University.

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Gao, P., Zeng, X., Zhang, L. et al. Overexpression of miR-378 Alleviates Chronic Sciatic Nerve Injury by Targeting EZH2. Neurochem Res 46, 3213–3221 (2021). https://doi.org/10.1007/s11064-021-03424-9

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  • DOI: https://doi.org/10.1007/s11064-021-03424-9

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