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

被引:6
作者
Wang, Han [1 ]
Sun, Yang [2 ,3 ]
Wu, Yu [1 ]
Shen, Yi-Jia [1 ]
Xia, Jun [1 ]
Xu, Ye-Hao [1 ]
Yue, Liang [1 ]
Sun, Li [1 ]
Li, Xiu-Juan [1 ]
Ma, Yu [1 ]
Xiong, Yuan-Chang [1 ]
Li, Dai [1 ]
机构
[1] Naval Med Univ, Changhai Hosp, Dept Anesthesiol, Changhai Rd 168, Shanghai 200433, Peoples R China
[2] Xian Med Univ, Dept Rehabil Med, Affiliated Hosp 2, Xian 710000, Shaanxi, Peoples R China
[3] Xian Phys Educ Univ, Xian 710000, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-30d; GAD67; Neuropathic pain; Vincristine; Neuroplasticity; SPINAL-CORD; GENE-TRANSFER; GABA; GLUTAMATE; ACID; GABAPENTIN; ACTIVATION; PREGABALIN; MANAGEMENT; MODEL;
D O I
10.1007/s11064-021-03462-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:481 / 492
页数:12
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