Identification of the transcription factor, AFF4, as a new target of miR-203 in CNS

MiR-203 was identified as a hub of a potential regulatory miRNA network in central nervous system. Overexpressing of miR-203 in the frontal cortex of C57BL/6J wild type mouse induced neurodegeneration by increasing the apoptotic pathway and neuron death. AFF4, a transcription factor, was identified as a new bona fida protein target of miR-203 in CNS. The miRNA:mRNA interaction of miR-203 and AFF4 was verified using Dural-luciferase assay. Down-regulated expression of AFF4 was induced by overexpressing miR-203 both in vitro and in vivo. Open field test, Y maze and Morris water maze test were conducted for the behavioral assessment of the mice with stereotactic injection of lentiviral vector overexpressing miR-203 in the hippocampus. No anxiety-like behavior or impaired cognition was noticed in these mice. Consistent with the results of the behavioral assessment, the electron micrograph and Nissl staining revealed no significant change in the synaptic density and no neuron injuries in the hippocampus of mice overexpressing miR-203, respectively. Our results indicated that instead of promoting neurodegenerative phenotype, a more profound function should be ascribed to miR-203 in regulating neuron behavioral activities and cognition. Neuron-type specific functions of miR-203 are likely to be executed via its various downstream protein interactors.