Oxaliplatin treatment impairs extension of sensory neuron neurites in vitro through miR-204 overexpression

Neurotoxicology
María José López-GonzálezAlexandre Favereaux

Abstract

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 da...Continue Reading

Citations

Sep 26, 2020·Journal of Cellular and Molecular Medicine·Xin WangTianyi Wang
Jun 2, 2020·Frontiers in Cellular Neuroscience·Ximena Paez-ColasanteEva L Feldman
Nov 15, 2020·Journal of Neuroscience Methods·Cynthia AbboudMarc Landry
Jul 1, 2021·Cell & Bioscience·Mei ZhangXin-Hua Liang

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