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Original Article| Volume 28, ISSUE 2, P468-475, March 2023

Protein tyrosine phosphatase non-receptor type 12 suppresses tumor progression in osteosarcoma cells

  • Xinwu Wang
    Affiliations
    Department of Orthopaedics, The First Hospital of Putian City, Putian, Fujian, 351199, China
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  • Xinwen Wang
    Affiliations
    Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China
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  • Jiankun Lai
    Affiliations
    Department of Orthopaedics, Dongguan People 's Hospital, Dongguan, Guangdong, 523059, China
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  • Weifeng Xu
    Affiliations
    Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450008, China
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  • Wenxiong Zhu
    Correspondence
    Corresponding author. Department of Orthopaedics, Dongguan People 's Hospital, 78# Wandao Road, Xinguyong Community, Wanjiang Street, Dongguan, Guangdong, 523059, China. Fax: +86 076928636300
    Affiliations
    Department of Orthopaedics, Dongguan People 's Hospital, Dongguan, Guangdong, 523059, China
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  • Guoxian Chen
    Correspondence
    Corresponding author. Department of Orthopaedics, the First Hospital of Putian City, 389# Longdejing Community, Nanmen West Road, Chengxiang District, Putian, Fujian, 351199, China. Fax: +86 05942280617
    Affiliations
    Department of Orthopaedics, The First Hospital of Putian City, Putian, Fujian, 351199, China
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      Abstract

      Background

      Protein tyrosine phosphatase non-receptor 12 (PTPN12) plays a prominent role in various cancers as a tumor suppressor. However, the expression of PTPN12 and its biological functions in osteosarcoma (OS) remains to be determined.

      Methods

      PTPN12 expression in OS was explored in public databases and detected by immunohistochemistry and Western blot. The cell viability was determined by Cell Counting Kit-8 (CCK-8) assay and colony formation. The cell migration and invasion were assessed by the Transwell assay. Flow cytometry analysis was applied to detect cell apoptosis and cell cycle distribution. To investigate the related mechanism, the levels of EGFR and downstream proteins were detected by Western blot.

      Results

      PTPN12 expression was significantly decreased in OS samples in GEO database and our hospital. OS cell lines in Cancer Cell Line Encyclopedia (CCLE) database and our cultured OS cells also demonstrated low PTPN12 expression. Lentivirus-induced overexpression of PTPN12 significantly inhibited the cell viability, migration and invasion of 143B and U2OS cells. The results of flow cytometry found that PTPN12 overexpression promoted cell apoptosis and induced cell cycle arrest at G1 phase in 143B and U2OS cells. The phosphorylation levels of EGFR and subsequent proteins of the PI3K/AKT and ERK pathways were inactivated as a result of PTPN12 overexpression in OS.

      Conclusion

      PTPN12 plays a tumor suppressive role in OS cells. Restoring of PTPN12 activity may provide new insights for the treatment of this disease.
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