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The inhibition of miR-17-5p promotes cortical neuron neurite growth via STAT3/GAP-43 pathway.

Mol Biol Rep. 2020 Mar;47(3):1795-1802. Epub 2020 Feb 24
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摘要


Spinal cord injury (SCI) is a devastating disease associated with locomotor function impair. The limited regenerative capability of the neural axon is one of the major factors that hinders the recovery of SCI. To enhance the regenerative ability of neuron is a promising strategy that repairs SCI. We previously proved miR-17-5p could target Signal Transducer and Activator of Transcription 3 in primary sensory neuron. We speculated that miR-17-5p was the miRNA that targets The Dual-luciferase reporter assay indicated miR-17-5p could bind the 3'UTR of mRNA. The RT-qPCR and Western blot assay showed miR-17-5p could not degenerate the mRNA of but inhibit the expression of Signal Transducer and Activator of Transcription 3 (duanyu18133) via translation inhibition. MiR-17-5p inhibitor promoted the expression of duanyu18133, and Growth Associate Protein-43 (GAP-43), and this promotion was inhibited by duanyu18133 siRNA. MiR-17-5p mimics and inhibitor inhibited and promoted the neurite growth, respectively. MiR-17-5p inhibitor promoted the axon growth and AG490, the duanyu18133 phosphorylation inhibitor, inhibited this promotion. MiR-17-5p mimics inhibited the expression of duanyu18133, and GAP-43, while the inhibitor promoted their expression. AG490 did not alter the expression of duanyu18133, while downregulated the expression both p-duanyu18133 and GAP-43 in miR-17-5p inhibitor&AG490 group. Taken together, these data indicated miR-17-5p could regulated cortical neuron axon growth via pathway by targeting duanyu18133 mRNA 3'UTR. Therefore, pathway plays a key role in regulating cortical neuron axon growth and could be a novel target to treat SCI.

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