ArticlePharmacogenomics and personalized medicine2024
Hsa_circ_0078767 Enhances Osteosarcoma Chemoresistance to Doxorubicin Through the Regulation of the miR-188-3p/GPX4 Axis.
Article in Pharmacogenomics and personalized medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Osteosarcoma (OS) is a primary malignancy of bone. The emergence of chemoresistance represents a persistent barrier to effective cancer patient care. This analysis sought to examine hsa_circ_0078767 as a mediator of doxorubicin (DOX) resistance in OS. Methods: Levels of hsa_circ_0078767, miR-188-3p, and glutathione peroxidase 4 (GPX4) in OS clinical tissue samples and cell lines were evaluated by quantitative polymerase chain reaction (qPCR) and Western blotting. Associations between hsa_circ_0078767 levels in clinical samples and patient overall survival were assessed with Kaplan-Meier curves. CCK-8 assays were utilized as a means of examining DOX half-inhibitory concentration (IC Results: OS patient tissues and cell lines resistant to DOX exhibited elevated hsa_circ_0078767 and GPX4 expression together with a reduction in miR-188-3p levels. Inhibiting hsa_circ_0078767 expression contributed to a profound decrease in the ability of OS tumors to resist DOX. Mechanistically, it was determined that hsa_circ_0078767 can enhance DOX chemoresistance through its ability to bind and sequester miR-188-3p, which otherwise negatively modulates GPX4 to enhance chemosensitivity. Accordingly, the sequestration of miR-188-3p by hsa_circ_0078767 led to the derepression and upregulation of GPX4. Conclusion: Hsa_circ_0078767 was found to modulate miR-188-3p/GPX4 signaling to enhance OS cell resistance to DOX treatment and facilitate disease progression. As such, hsa_circ_0078767 may represent a valuable biomarker or target for use in the context of OS patient management.
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