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Published on: May 3, 2021
DLX2 promotes osteosarcoma epithelial-mesenchymal transition and doxorubicin resistance by enhancing HOXC8-CDH2 axis
Boya Zhang1, Xinhui Du1, Yichao Fan1
1Department of Bone and Soft Tissue Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China.
Abstract:
Metastasis and doxorubicin resistance are challenges in the clinical diagnosis and treatment of osteosarcoma, the mechanisms underlying these phenomena remain unclear. In this study, we found that DLX2 is highly expressed in metastatic osteosarcoma and is closely related to clinical prognosis. Knockdown of DLX2 inhibited tumor proliferation and migration in vitro and inhibited tumor growth in vivo. Mechanistically, we found that DLX2 enhanced the repression of CDH2 transcription by binding to HOXC8, thereby promoting the epithelial-mesenchymal transition in osteosarcoma cells. Through subsequent exploration, we found that targeting DLX2/HOXC8 signaling significantly restores the sensitivity of osteosarcoma cells to doxorubicin. In conclusion, our findings demonstrate that DLX2 may enhance the transcriptional regulation of CDH2 through interacting with HOXC8, which in turn promotes epithelial-mesenchymal transition and doxorubicin resistance in osteosarcoma. These findings hold great potential for clinical application and may guide the development of novel targeted therapies for osteosarcoma.
Insights
Discover how DLX2 promotes osteosarcoma metastasis and doxorubicin resistance by interacting with HOXC8 to regulate CDH2. Targeting this pathway may restore drug sensitivity and improve osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma metastasis and doxorubicin resistance present significant clinical challenges.
- The underlying molecular mechanisms driving these phenomena are not fully understood.
Purpose of the Study:
- To investigate the role of DLX2 in osteosarcoma metastasis and doxorubicin resistance.
- To elucidate the molecular mechanisms by which DLX2 influences these processes.
Main Methods:
- Assessed DLX2 expression in osteosarcoma tissues and correlated with prognosis.
- Performed in vitro and in vivo experiments involving DLX2 knockdown.
- Investigated the interaction between DLX2, HOXC8, and CDH2 transcription.
- Evaluated the effect of targeting DLX2/HOXC8 signaling on doxorubicin sensitivity.
Main Results:
- DLX2 is highly expressed in metastatic osteosarcoma and linked to poor prognosis.
- DLX2 knockdown inhibited osteosarcoma cell proliferation, migration, and tumor growth.
- DLX2 interacts with HOXC8 to repress CDH2 transcription, promoting epithelial-mesenchymal transition.
- Targeting DLX2/HOXC8 signaling restored doxorubicin sensitivity in osteosarcoma cells.
Conclusions:
- DLX2 promotes osteosarcoma epithelial-mesenchymal transition and doxorubicin resistance via HOXC8-mediated CDH2 repression.
- The DLX2/HOXC8 signaling pathway is a potential therapeutic target for overcoming osteosarcoma metastasis and drug resistance.
