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SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma

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Abstract

Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. Patients with NF1 often have complications with tumors, such as neurofibroma. In order to investigate the pathogenesis of human neurofibroma, a systematic comparison of protein expression levels between Schwann cell-like sNF96.2 cells, which originated from malignant peripheral nerve sheath tumors (MPNST), and normal Schwann cells was performed using 4-D label-free proteomic analysis. In addition, the expression levels and localization of dysregulated proteins were confirmed using a Gene Expression Omnibus (GEO) transcriptomic dataset, Western blot analysis, and immunofluorescence labeling. The effects of SRY-box transcription factor 9 (SOX9) in the neurofibroma and surrounding microenvironment were evaluated in vivo using a tumor transplantation model. The present study observed that SOX9 and procollagen C-endopeptidase enhancer (PCOLCE) were significantly altered. NF1 mutation promoted the nuclear translocation and transcriptional activity of SOX9 in neurofibromas. SOX9 increased collagen VI secretions by enhancing the activation of PCOLCE in neurofibroma cells. These findings might provide new perspectives on the pathophysiological significance of SOX9 in neurofibromas and elucidate a novel molecular mechanism underlying neurofibromas.

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Data Availability

The datasets generated and/or analyzed during this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank Jiali Zhang for helping in revising grammar and sentences.

Funding

This study was supported by grants from the National Natural Science Foundation of China (81960541), the Natural Science Foundation of Gansu Province (22JR5RA959/22JR5RA966/2ZD6FA021-4), Medical Innovation and Development Project of Lanzhou University (lzuyxcx-2022-170), the Lanzhou Science and Technology Bureau Project (2021-RC-97), Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital (Grant Numbers: CY2021-MS-A09/A19). Cuiying Scientific Training Program for Undergraduates of Lanzhou University Second Hospital (CYXZ-01/CYXZ2020-08), and Cuiying Graduate Supervisor Applicant Training Program (201803/CYDSPY202-002).

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  1. Xuan Yao and Bo Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China

    Xuan Yao, Bo Wang, Yuanping Su, Qiao Li, Qiang Dong, Hang Yin, Yawen Pan & Guoqiang Yuan

  2. The Second Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China

    Xuan Yao, Bo Wang, Yuanping Su, Qiao Li, Jianying Wang, Yawen Pan & Guoqiang Yuan

  3. Institute of modern physics, Chinese Academy of Science, Lanzhou, 730000, Gansu, China

    Zhitong Bing

  4. Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, 516000, China

    Zhitong Bing

Authors
  1. Xuan Yao
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Contributions

XY performed experiments, analyzed data, and wrote the draft. BW and YS performed the experiments and analyzed the data. ZB performed the bioinformatics analysis. QL, QD, HY, and JW performed the experiments. YP conceived and designed the experiments. GY conceived and designed experiments, analyzed data, and revised the manuscript.

Corresponding authors

Correspondence to Yawen Pan or Guoqiang Yuan.

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Yao, X., Wang, B., Su, Y. et al. SOX9 Promotes Collagen VI Secretion by Upregulating PCOLCE in Neurofibroma. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04036-4

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