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DownRegulated SOX4 Expression Suppresses Cell Proliferation, Migration, and Induces Apoptosis in Osteosarcoma In Vitro and In Vivo

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Abstract

The SOX4 transcription factor is involved in various cellular processes, such as embryonic development and differentiation. Deregulated expression of Sox4 in several human cancers has been reported to date, but its biological functions in the progression of osteosarcoma remain unclear. In this study, we found that the expression levels of SOX4 protein were significantly higher in high-grade osteosarcoma tissues and metastatic osteosarcoma tissues. Its overexpression was associated with poor prognosis in osteosarcoma. Knockdown of the SOX4 gene in the osteosarcoma cell lines resulted in decreased cell proliferation, migration, invasion, and induced apoptosis. After SOX4 gene silencing, the protein expression levels of Bax, Caspase-3, and P53 in osteosarcoma cells were significantly elevated, while the protein expression levels of Bcl-2, MMP2, and MMP9 were obviously decreased. In vivo analysis in nude mice further confirmed that knockdown of SOX4 suppressed tumor growth. In conclusion, SOX4 appears to be an important tumor oncogene in the regulation of osteosarcoma cell proliferation, apoptosis, and invasion, and it may be a potential target for effective osteosarcoma therapy.

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Acknowledgements

This study was supported in part by a Grant from key project of Shanghai Science and Technology Commission (No. 11411950400).

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Author notes

  1. Dong Chen, Chuanzhen Hu and Gen Wen contributed to this work equally as first author.

Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215003, China

    Dong Chen, Gen Wen & Huilin Yang

  2. Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

    Dong Chen, Gen Wen, Qingcheng Yang & Changqing Zhang

  3. Department of Orthopaedic Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai, 200072, China

    Chuanzhen Hu

  4. Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai, 200072, China

    Chuanzhen Hu

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  1. Dong Chen
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Correspondence to Huilin Yang.

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Conflict of interest

Dong Chen, Chuanzhen Hu, Gen Wen, Qingcheng Yang, Changqing Zhang, and Huilin Yang declare no competing financial interests.

Human and Animal Rights

This study was approved by the ethics committee of Shanghai Sixth People ‘s Hospital. All experimental procedures were conducted in conformity with institutional guidelines for the care and use of laboratory animals in Shanghai Sixth People’s Hospital, Shanghai, China and conformed to the National Institutes of Regulations for the Administration of Affairs Concerning Experimental Animals.

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Informed consent was obtained from all individual participants included in the study.

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Chen, D., Hu, C., Wen, G. et al. DownRegulated SOX4 Expression Suppresses Cell Proliferation, Migration, and Induces Apoptosis in Osteosarcoma In Vitro and In Vivo. Calcif Tissue Int 102, 117–127 (2018). https://doi.org/10.1007/s00223-017-0340-x

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  • DOI: https://doi.org/10.1007/s00223-017-0340-x

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