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MiR-30d Participates in Vincristine-Induced Neuropathic Pain by Down-Regulating GAD67

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Abstract

Vincristine is a common chemotherapeutic agent in cancer treatment, while it often causes chemotherapy-induced peripheral neuropathy(CIPN), which brings patients a great disease burden and associated economic pressure. The mechanism under CIPN remains mostly unknown. The previous study has shown that cell-type-specific spinal synaptic plasticity in the dorsal horn plays a pivotal role in neuropathic pain. Downregulation of GABA transmission, which mainly acts as an inhibitory pathway, has been reported in the growing number of research. Our present study found that GAD67, responsible for > 90% of basal GABA synthesis, is down-regulated, while its relative mRNA remains unchanged in vincristine-induced neuropathy. Considering microRNAs (miRNAs) as a post-transcription modifier by degrading targeted mRNA or repressing mRNA translation, we performed genome-wide miRNA screening and revealed that miR-30d might contribute to GAD67 down-regulation. Further investigation confirmed that miR-30d could affect the fluorescence activity of GAD67 by binding to the 3 'UTR of the GAD67 gene, and intrathecal injection of miR-30d antagomir increased the expression of GAD67, partially rescued vincristine-induced thermal hyperalgesia and mechanical allodynia. In summary, our study revealed the molecule interactions of GAD67 and miR-30d in CIPN, which has not previously been discussed in the literature. The results give more profound insight into understanding the CIPN mechanism and hopefully helps pain control.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

This work has not been previously published and has not been submitted elsewhere for consideration. This study was funded by the National Natural Science Foundation of China (81600955, 81971048), Shanghai Pujiang Program (2020PJD059), "Deep Blue 123" Military Medical Research Special Key Research Project(2019YSL008), Natural Science Foundation of Shaanxi Province Department of Science and Technology (2018JM7052) and Scientific Research Fund Project of Shaanxi Province Department of Education (18JK0675).

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  1. Han Wang, Yang Sun and Yu Wu have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Changhai Hospital, Naval Medical University, Changhai Rd.168, Shanghai, 200433, China

    Han Wang, Yu Wu, Yi-Jia Shen, Jun Xia, Ye-Hao Xu, Liang Yue, Li Sun, Xiu-Juan Li, Yu Ma, Yuan-Chang Xiong & Dai Li

  2. Department of Rehabilitation Medicine, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, 710000, Shaanxi, China

    Yang Sun

  3. Xi’an Physical Education University, Xi’an, 710000, Shaanxi, China

    Yang Sun

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  1. Han Wang
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Correspondence to Yuan-Chang Xiong or Dai Li.

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Wang, H., Sun, Y., Wu, Y. et al. MiR-30d Participates in Vincristine-Induced Neuropathic Pain by Down-Regulating GAD67. Neurochem Res 47, 481–492 (2022). https://doi.org/10.1007/s11064-021-03462-3

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