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

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Abstract

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 (STAT3) in primary sensory neuron. We speculated that miR-17-5p was the miRNA that targets STAT3. The Dual-luciferase reporter assay indicated miR-17-5p could bind the 3′UTR of STAT3 mRNA. The RT-qPCR and Western blot assay showed miR-17-5p could not degenerate the mRNA of STAT3, but inhibit the expression of Signal Transducer and Activator of Transcription 3 (STAT3) via translation inhibition. MiR-17-5p inhibitor promoted the expression of STAT3, phosphorylated-STAT3 (p-STAT3) and Growth Associate Protein-43 (GAP-43), and this promotion was inhibited by STAT3 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 STAT3 phosphorylation inhibitor, inhibited this promotion. MiR-17-5p mimics inhibited the expression of STAT3, p-STAT3 and GAP-43, while the inhibitor promoted their expression. AG490 did not alter the expression of STAT3, while downregulated the expression both p-STAT3 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 STAT3/GAP-43 pathway by targeting STAT3 mRNA 3′UTR. Therefore, miR-17-5p/STAT3/GAP-43 pathway plays a key role in regulating cortical neuron axon growth and could be a novel target to treat SCI.

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Acknowledgements

We are grateful to Dr. Yanjun Zhang and postgraduate student Shichang Yang for their assistance at cell culture and detection. This work was supported by the General Program of Natural Science Foundation of Hebei Province of China (Grant Number H2017101030), the Medical Science and Technology Youth Cultivation Project of the Chinese People’s Liberation Army (Grant Numbers 16QNP074 and 13QNP017), the Research and Development of Science and Technology Program Supported by Chengde Government (Grant Numbers 201606A062, 201701A125, 201701A127), the Key Program of Medical Science Foundation of Hebei province of China (Grant Number 20190189).

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  1. Liang Zhang, Zhijie Wang, Bo Li, Ziwei Xia, and Xin Wang have contributed equally to this article.

Authors and Affiliations

  1. Department of Orthopedics, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China

    Liang Zhang, Ziwei Xia & Kai Wang

  2. Department of Pediatric Internal Medicine, Affiliated Hospital of Chengde Medical University, Chengde, 067000, Hebei, People’s Republic of China

    Zhijie Wang

  3. Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China

    Bo Li

  4. Chengde Medical University, Chengde, 067000, Hebei, People’s Republic of China

    Xin Wang & Meiling Zhang

  5. Department of Orthopedics, The 981st Hospital of the Chinese People’s Liberation Army, Chengde, 067000, Hebei, People’s Republic of China

    Yucai Xiu, Zheng Zhang, Wenhua Li & Tianyi Wang

  6. Department of Orthopedics, Chengde Central Hospital, Chengde, 067000, Hebei, People’s Republic of China

    Chuanjie Chen

  7. Department of Anesthesiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China

    Hong Song

  8. Leukemia Center, Peking Union of Medical College, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Tianjin, 30020, People’s Republic of China

    Mei Yu & Xiaoling Guo

  9. Department of Neurology, The 981st Hospital of the Chinese People’s Liberation Army, Chengde, 067000, Hebei, People’s Republic of China

    Xiaoling Guo

  10. Laboratory of Spinal Cord Injury and Rehabilitation, Chengde Medical University, Chengde, 067000, Hebei, People’s Republic of China

    Liqun Ren

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  1. Liang Zhang
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Contributions

Conceptualization, XLG, KW, TYW and ZJW; Methodology, YCX, ZZ, CJC and MLZ; Software, HS; Validation, WHL and MY; Formal Analysis, YCX; Investigation, MLZ; Data Curation, LZ; Writing-Original Draft Preparation, BL, LZ, ZWX and XW; Writing-Review & Editing, TYW and KW; Visualization, ZJW; Supervision, XLG, KW, TYW and ZJW; Project Administration, TYW; Funding Acquisition, TYW, ZZ, CJC and WHL. All authors read and approved the final manuscript.

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Correspondence to Kai Wang, Xiaoling Guo, Liqun Ren or Tianyi Wang.

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Zhang, L., Wang, Z., Li, B. et al. The inhibition of miR-17-5p promotes cortical neuron neurite growth via STAT3/GAP-43 pathway. Mol Biol Rep 47, 1795–1802 (2020). https://doi.org/10.1007/s11033-020-05273-1

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