MicroRNA-30b regulates expression of the sodium channel Nav1.7 in nerve injury-induced neuropathic pain in the rat.
MicroRNA-30b regulates expression of the sodium channel Nav1.7 in nerve injury-induced neuropathic pain in the rat.
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MicroRNA-30b 在神经损伤引起的大鼠神经性疼痛中调节钠通道 Nav1.7 的表达。
DOI：
10.1177/1744806916671523
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Zang W
中科院分区：
文献类型：
--
作者：
Shao J;Cao J;Wang J;Ren X;Su S;Li M;Li Z;Zhao Q;Zang W
参与疼痛通路的电压门控钠通道已成为疼痛障碍治疗干预的主要靶点。由SCN9A编码的河豚毒素敏感的电压门控钠通道亚型Nav1.7主要表达于背根神经节的痛敏神经元，在伤害性感受中起重要作用。MicroRNAs是高度保守的非编码小RNA。通过与靶mRNAs的3‘端非翻译区结合，microRNAs诱导蛋白质翻译的切割和/或抑制。基于TargetScan软件的生物信息学分析，我们确定miR-30b直接针对SCN9A。为了探讨Nav1.7和miR-30b在神经病理性疼痛中的作用，我们在大鼠备用神经损伤模型上观察了miR-30b过表达或敲除对背根神经节Nav1.7表达的影响。结果表明，在备用神经损伤大鼠背根神经节，miR-30b和Nav1.7的表达分别下调和上调。MIR-30b在备用神经损伤大鼠中的过度表达抑制了SCN9A的转录，从而导致疼痛缓解。此外，miR-30b基因敲除显著增加了幼稚大鼠对疼痛的过敏。我们还观察到miR-30b降低了PC12细胞中Nav1.7的表达。综上所述，我们的结果表明miR-30b通过调节Nav1.7的表达在神经病理性疼痛中发挥重要作用。因此，miR-30b可能是治疗慢性神经病理性疼痛的一个有前途的靶点。
Voltage-gated sodium channels, which are involved in pain pathways, have emerged as major targets for therapeutic intervention in pain disorders. Nav1.7, the tetrodotoxin-sensitive voltage-gated sodium channel isoform encoded by SCN9A and predominantly expressed in pain-sensing neurons in the dorsal root ganglion, plays a crucial role in nociception. MicroRNAs are highly conserved, small non-coding RNAs. Through binding to the 3′ untranslated region of their target mRNAs, microRNAs induce the cleavage and/or inhibition of protein translation. Based on bioinformatics analysis using TargetScan software, we determined that miR-30b directly targets SCN9A. To investigate the roles of Nav1.7 and miR-30b in neuropathic pain, we examined changes in the expression of Nav1.7 in the dorsal root ganglion by miR-30b over-expression or knockdown in rats with spared nerve injury. Our results demonstrated that the expression of miR-30b and Nav1.7 was down-regulated and up-regulated, respectively, in the dorsal root ganglion of spared nerve injury rats. MiR-30b over-expression in spared nerve injury rats inhibited SCN9A transcription, resulting in pain relief. In addition, miR-30b knockdown significantly increased hypersensitivity to pain in naive rats. We also observed that miR-30b decreased Nav1.7 expression in PC12 cells. Taken together, our results suggest that miR-30b plays an important role in neuropathic pain by regulating Nav1.7 expression. Therefore, miR-30b may be a promising target for the treatment of chronic neuropathic pain.
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影响因子：
64.5
作者：
Lee JH;Park CK;Chen G;Han Q;Xie RG;Liu T;Ji RR;Lee SY
通讯作者：
Lee SY
影响因子：
3.5
作者：
Ho, Cojen;O'Leary, Michael E.
通讯作者：
O'Leary, Michael E.
影响因子：
4.4
作者：
Dabby, Ron;Sadeh, Menachem;Leshinsky-Silver, Esther
通讯作者：
Leshinsky-Silver, Esther
影响因子：
3.3
作者：
Chattopadhyay M;Zhou Z;Hao S;Mata M;Fink DJ
通讯作者：
Fink DJ
影响因子：
4.8
作者：
Hong, SS;Morrow, TJ;Wiley, JW
通讯作者：
Wiley, JW