Single-cell analysis links DCUN1D5 to immune remodeling and cisplatin resistance in recurrent osteosarcoma
Abstract Cisplatin is the primary chemotherapeutic agent for osteosarcoma. However, a significant proportion of patients develop resistance post-treatment, leading to disease recurrence and presenting profound clinical challenges. To understand the mechanisms underlying osteosarcoma recurrence and c...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08409-w |
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| Summary: | Abstract Cisplatin is the primary chemotherapeutic agent for osteosarcoma. However, a significant proportion of patients develop resistance post-treatment, leading to disease recurrence and presenting profound clinical challenges. To understand the mechanisms underlying osteosarcoma recurrence and cisplatin resistance, particularly from the tumor microenvironment perspective, we consolidated numerous single-cell RNA sequencing datasets, offering an encompassing insight into the osteosarcoma microenvironment. When juxtaposing scRNA-seq with bulk RNA-seq data, we observed a strong correlation between high DCUN1D5 expression in osteosarcoma and patient survival. This gene amplifies osteosarcoma’s anti-apoptotic, invasive, stem-cell-like traits and PI3K/AKT/GSK3β pathway phosphorylation and fosters cisplatin resistance. Subsequent research revealed that cisplatin-resistant osteosarcoma cells excrete DCUN1D5-rich exosomes, facilitating the maturation of osteoclast precursors. Excessive osteoclast activity is a pivotal contributor to osteosarcoma recurrence and resistance. Given these insights, DCUN1D5 is a promising therapeutic target for osteosarcoma recurrence and drug resistance. |
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| ISSN: | 2399-3642 |