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Updated: Jun 23, 2025

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
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Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

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EYA4 reduces chemosensitivity of osteosarcoma to doxorubicin through DNA damage repair

Wei Heng1, Tianfu Wang1, Feilong Wei1

  • 1Department of Orthopedics, Tangdu Hospital, Air Force Military Medical University, Xi'an 710038, China.

Biochemical Pharmacology
|June 14, 2024
PubMed

Insights

Eyes Absent 4 (EYA4) promotes drug resistance in osteosarcoma (OS) by enhancing DNA repair. Reducing EYA4 levels can re-sensitize OS cells to chemotherapy, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Eyes Absent 4 (EYA4) is implicated in tumor cell proliferation, migration, and chemoresistance.
  • Understanding EYA4's role in drug resistance is crucial for developing effective osteosarcoma (OS) treatments.

Purpose of the Study:

  • To investigate the role of EYA4 in conferring doxorubicin (DOX) resistance in osteosarcoma (OS).
  • To elucidate the underlying molecular mechanisms by which EYA4 influences chemoresistance in OS.

Main Methods:

  • Bioinformatics, histological, and cellular analyses were employed to assess EYA4 expression in OS tissues and cells.
  • In vitro and in vivo experiments involving EYA4 knockdown and overexpression were conducted.
  • Mechanistic studies explored EYA4's interaction with DNA damage repair (DDR) pathways, including histone H2AX.

Main Results:

  • EYA4 expression was significantly higher in OS tissues and drug-resistant OS cells compared to healthy controls and sensitive cells.
  • EYA4 knockdown increased OS sensitivity to doxorubicin (DOX), while EYA4 overexpression decreased sensitivity.
  • EYA4 was found to directly interact with histone H2AX, activating the DNA double-strand break (DSB) repair pathway.

Conclusions:

  • EYA4 plays a critical role in mediating doxorubicin (DOX) resistance in osteosarcoma (OS) by promoting DNA damage repair (DDR).
  • Targeting EYA4 presents a promising strategy for overcoming chemoresistance in osteosarcoma patients.
Keywords:
ChemoresistanceDNA damage repairDoxorubicinEYA4Osteosarcoma

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