miR-21 and miR-222 inhibit apoptosis of adult dorsal root ganglion neurons by repressing TIMP3 following sciatic nerve injury

• miR-21 and miR-222 were among 13 differentially expressed miRNAs in rat DRGs after sciatic nerve injury.
• Over-expression of miR-21 and miR-222 inhibited apoptosis of cultured DRG neurons by targeting TIMP3.
• IL-6 up-regulated the miR-21 expression in cultured DRG neurons.

MicroRNAs (miRNAs or miRs) are involved in phenotype modulation of neural cells after peripheral nerve injury. The effects of miRNAs on the survival of dorsal root ganglion (DRG) neurons, however, have not yet been well understood. In this study, microarray profiling indicated that 13 miRNAs were differentially expressed in rat DRGs (L4-L6) during the initial 7 d period post sciatic nerve transection, and that the expressions of miR-21 and miR-222 (2 out of the 13 miRNAs) were continually increased over the time period. Tissue inhibitor of metalloproteinase 3 (TIMP3), a pro-apoptotic protein in various cancer cells, was identified as a common target of miR-21 and miR-222. Over-expression of miR-21 and miR-222 inhibited cell apoptosis and enhanced cell viability in cultured DRG neurons. IL-6 could induce up-regulation of miR-21 expression. All the results showed that miR-21 and miR-222 inhibited neuronal apoptosis at least partially through suppressing TIMP3 after peripheral nerve injury.