AI Article Synopsis
- Osteosarcoma (OS) is the most common type of bone cancer in young people, highlighting the urgent need for new treatment options.
- In this study, researchers identified DNA polymerase epsilon 2 (POLE2) as overexpressed in OS tissues, and reducing its levels slowed OS cell growth and migration while increasing cell death.
- Further analysis showed that POLE2 promotes CD44 expression by preventing its degradation and activates the Rac signaling pathway, suggesting that targeting the POLE2/CD44 interaction could be a promising approach for treating OS.
Article Abstract
Osteosarcoma (OS) is the most prevalent primary malignancy of bone in children and adolescents. It is extremely urgent to develop a new therapy for OS. In this study, the GSE14359 chip from the GEO database was used to screen differentially expressed genes in OS. DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferation and migration of OS cells in vitro, as well as the growth of tumors in vivo, while the apoptosis rate was increased. Bioinformatics analysis revealed that CD44 and Rac signaling pathway were the downstream molecule and pathway of POLE2, which were inhibited by knockdown of POLE2. POLE2 reduced the ubiquitination degradation of CD44 by acting on MDM2. Moreover, knockdown of CD44 inhibited the tumor-promoting effects of POLE2 overexpression on OS cells. In conclusion, POLE2 augmented the expression of CD44 via inhibiting MDM2-mediated ubiquitination, and then activated Rac signaling pathway to influence the progression of OS, indicating that POLE2/CD44 might be potential targets for OS treatment.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11021398 | PMC |
| http://dx.doi.org/10.1038/s41420-024-01875-x | DOI Listing |
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