MicroRNA‐212 inhibits oligodendrocytes during maturation by down‐regulation of differentiation‐associated gene expression

MicroRNA‐212 (mir‐212) has been reported to regulate neuronal development and functioning. However, its expression and function in glia are not yet known. Here, we demonstrate that the level of microRNA‐212 (mir‐212) was reduced in spinal cord lesion site at 1 week and 1 month after a contusive spinal cord injury. In addition to its expression in neurons, mir‐212 expression was detected in oligodendrocytes (OLGs) and glial progenitor cells (GPCs) in adult CNS. The addition of antagomir‐212 to reduce mir‐212 expression enabled to improve the cell process outgrowth of OLGs along with the up‐regulation of the genes associated with OLG differentiation and maturation, including OLIG1, SOX10, myelin basic protein (MBP), and proteolipid protein 1 (PLP1). In contrast, these genes were significantly down‐regulated by an increased expression of mir‐212 in GPCs or in OLG progenitor cells (OPCs) through lentivirus‐mediated gene delivery approach. Moreover, we found that PLP1 was the direct target molecule of mir‐212. Furthermore, mir‐212 over‐expression diminished the protein production of OLGs markers including 2′,3′‐cyclic‐nucleotide 3′‐phosphodiesterase (CNPase), MBP, and PLP. Additionally, mir‐212 over‐expression decreased the number of mature OLGs expressing MBP, and the expression of galactocerebroside (GC). Complementary studies in a hippocampal neuron‐OLG co‐culture model and an ex vivo cerebellar slice system indicated that OLGs derived from GPCs with mir‐212 over‐expression exhibited decreased ability to interact with neuronal axons. Collectively, our findings demonstrate that mir‐212 repressed the expression of OLG maturation‐associated proteins and inhibited OLG cell process extension, indicating that mir‐212 has negative regulatory effect on OLG lineage progression. MicroRNA‐212 (mir‐212) can regulate neuronal development and functioning. However, its expression and function in glia are not yet known. This report shows that spinal cord injury and interferon‐γ (other undefined molecules) can reduce mir‐212 expression in oligodendrocytes. Furthermore, mir‐212 can suppress oligodendrocyte maturation with the reduction in oligodendrocyte differentiation‐associated genes (OLIG1, OLIG2, and SOX10) and maturation proteins (MBP and PLP).