DLX2 promotes osteosarcoma epithelial-mesenchymal transition and doxorubicin resistance by enhancing HOXC8-CDH2 axis.
iScience
; 26(11): 108272, 2023 Nov 17.
Article
em En
| MEDLINE
| ID: mdl-38026218
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.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
IScience
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China