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Published on: May 3, 2021
Deduction of CDC42EP3 suppress development and progression of osteosarcoma
Peng Xu1, Xiaoxi Li2, Chao Tang3
1Department of Sports Medicine, The First Hospital of Jilin University, Jilin University, 71 Xinmin Street, Chaoyang District, Changchun City, Jilin Province, China.
Background:
Osteosarcoma is a disease with high mortality of malignant tumors in children and adolescents. CDC42 effector protein 3 (CDC42EP3) has been reported to be associated with human cancer cell progression. This study aimed to investigate the biological function and preliminary molecular mechanism of CDC42EP3 in osteosarcoma.
Methods:
CDC42EP3 expression in osteosarcoma was analyzed by immunohistochemical (IHC) staining. Secondly, the biological effects of CDC42EP3 in osteosarcoma cells was determined by loss/gain-of-function assays in vitro and in vivo.
Results:
CDC42EP3 expression was higher in osteosarcoma tissue than in noncancerous tissue. The expression of CDC42EP3 was positively correlated with age, pathological stage and grade of patients with osteosarcoma. Furthermore, downregulation of CDC42EP3 suppressed tumor progression by inhibiting proliferation, migration and inducing apoptosis in vivo. Importantly, knockdown of CDC42EP3 reduced the expression of interstitial markers (N-cadherin, Vimentin and Snail) and increased the expression of epithelial markers (E-cadherin). In addition, CDC42EP3 knockdown downregulated PI3K and reduced the phosphorylation levels of AKT and mTOR. The mice xenograft model further confirmed that CDC42EP3 knockdown inhibited osteosarcoma growth in vitro.
Conclusions:
In summary, these findings highlighted the significance of CDC42EP3 in tumor progression, which implicated CDC42EP3 as a promising candidate molecular target for osteosarcoma therapy.
Insights
CDC42 effector protein 3 (CDC42EP3) promotes osteosarcoma progression by increasing proliferation and migration. Downregulating CDC42EP3 inhibits tumor growth, suggesting it as a potential therapeutic target for osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Osteosarcoma is a highly fatal cancer in children and adolescents.
- CDC42 effector protein 3 (CDC42EP3) is implicated in human cancer progression.
- The role of CDC42EP3 in osteosarcoma remains largely uncharacterized.
Purpose of the Study:
- To investigate the biological function of CDC42EP3 in osteosarcoma.
- To elucidate the preliminary molecular mechanisms of CDC42EP3 in osteosarcoma.
- To evaluate CDC42EP3 as a potential therapeutic target for osteosarcoma.
Main Methods:
- Immunohistochemical (IHC) staining to analyze CDC42EP3 expression in osteosarcoma tissues.
- In vitro and in vivo loss/gain-of-function assays to assess the biological effects of CDC42EP3.
- Western blotting to examine the expression of epithelial-mesenchymal transition (EMT) markers and the PI3K/AKT/mTOR pathway.
Main Results:
- CDC42EP3 expression is elevated in osteosarcoma tissues and correlates with advanced stage and grade.
- Downregulation of CDC42EP3 inhibits osteosarcoma cell proliferation, migration, and induces apoptosis.
- CDC42EP3 knockdown reduces mesenchymal markers, increases epithelial markers, and downregulates the PI3K/AKT/mTOR pathway.
Conclusions:
- CDC42EP3 plays a significant role in promoting osteosarcoma progression.
- CDC42EP3 inhibition suppresses tumor growth and EMT.
- CDC42EP3 represents a promising molecular target for osteosarcoma therapy.
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