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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Article info
Publication history
Accepted:
December 22,
2021
Received in revised form:
December 15,
2021
Received:
August 30,
2021
Identification
Copyright
© 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.