miR‐22‐3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis

Abstract Spinal cord injury (SCI) is a devastating disease. Strategies that enhance the intrinsic regenerative ability are very important for the recovery of SCI to radically prevent the occurrence of sensory disorders. Epidermal growth factor (EGF) showed a limited effect on the growth of primary sensory neuron neurites due to the degradation of phosphorylated‐epidermal growth factor receptor (p‐EGFR) in a manner dependent on Casitas B‐lineage lymphoma (CBL) (an E3 ubiquitin‐protein ligase). MiR‐22‐3p predicted from four databases could target CBL to inhibit the expression of CBL, increase p‐EGFR levels and neurites length via STAT3/GAP43 pathway rather than Erk1/2 axis. EGF, EGFR, and miR‐22‐3p were downregulated sharply after injury. In vivo miR‐22‐3p Agomir application could regulate CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis, and restore spinal cord sensory conductive function. This study clarified the mechanism of the limited promotion effect of EGF on adult primary sensory neuron neurite and targeting miR‐22‐3p could be a novel strategy to treat sensory dysfunction after SCI.