Faculty, Staff and Student Publications

Publication Date

11-17-2023

Journal

iScience

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.

Keywords

Cancer, Molecular biology, Pathophysiology

DOI

10.1016/j.isci.2023.108272

PMID

38026218

PMCID

PMC10651674

PubMedCentral® Posted Date

10-19-2023

PubMedCentral® Full Text Version

Post-print

fx1 (1).jpg (252 kB)
Graphical Abstract

Published Open-Access

yes

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