Oxaliplatin is a platinum-based drug used in the treatment of gastric cancers. Oxaliplatin treatment induces sensory neuropathy characterized by cold hypersensibility in the acute phase and sensory impairment when the neuropathy becomes chronic. In order to determine the effect of oxaliplatin on sensory neurons, we used an in vitro model in which oxaliplatin treatment reduced arborization of dorsal root ganglia neurons in a dose-dependent manner. Moreover, we characterized the role of microRNAs in oxaliplatin induced-neuropathy. In particular, we focused on microRNAs that control the expression of axon guidance molecules, and therefore, regulate neurite arborization. As a result, we highlighted the upregulation of miR-204, a microRNA that controls the expression of PlexinA2, a semaphorin receptor involved in neurite guidance. Interaction of miR-204 and Plexin A2 was confirmed by luciferase assay. In addition, overexpression of miR-204 in dorsal root ganglia neuron cultures reduced length and extension of neurites and also reduced Plexin A2 labelling without increasing apoptosis rate. On the other hand, sequestration of miR-204 by a specific microRNA sponge increases neurite length and PlexinA2 expression. Taken together, our data indicate that oxaliplatin impairs sensory neurons arborization through up-regulation of miR-204 that decreases PlexinA2 expression and neurite length.

奥沙利铂是用于治疗胃癌的铂基药物。奥沙利铂治疗可诱发感觉神经病，其特征是在急性期出现冷超敏反应，而当神经病变为慢性时会导致感觉障碍。为了确定奥沙利铂对感觉神经元的作用，我们使用了体外奥沙利铂治疗以剂量依赖性方式减少背根神经节神经元的乔化的模型。此外，我们表征了microRNA在奥沙利铂诱导的神经病中的作用。特别是，我们专注于控制轴突导向分子表达并因此调控神经突乔化的microRNA。结果，我们强调了miR-204的上调，miR-204是一种微神经，它控制PlexinA2的表达，PlexinA2是参与神经突引导的信号量受体。荧光素酶测定证实了miR-204和Plexin A2的相互作用。此外，在背根神经节神经元培养物中miR-204的过表达减少了神经突的长度和延伸，并且在不增加细胞凋亡率的情况下减少了Plexin A2标记。另一方面，特定的microRNA海绵隔离miR-204会增加神经突长度和PlexinA2表达。两者合计，我们的数据表明，奥沙利铂通过上调miR-204从而降低PlexinA2表达和神经突长度而损害感觉神经元的融合。