| 项目编号 |
PRJCA016838 |
| 项目标题 |
YBX1 recognizes m5C modifications of CHD3 mRNA to promote HR repair and enhance ovarian cancer cell resistance to platinum-induced stress |
| 涉及领域 |
Medical |
| 数据类型 |
Epigenomics
Transcriptome or Gene expression
Genome sequencing
|
| 物种名称 |
Homo sapiens
|
| 描述信息 |
Platinum-based drug chemotherapy causes genetic damage and induces apoptosis in ovarian cancer cells. Enhancing the ability to resist platinum drug-induced DNA damage and apoptotic stress is critical for tumor cells to acquire for drug resistance. Here, we found that Y-box binding protein 1 (YBX1) was highly expressed in cisplatin-resistant patient-derived organoids (PDOs) and was a crucial gene for alleviating platinum-induced stress and maintaining drug resistance characteristics in ovarian cancer cells. Mechanistically, YBX1 recognized m5C modifications in CHD3 mRNA and recruited PABPC1 protein to maintain mRNA stability and protein expression. This enhanced chromatin accessibility and improved the efficiency of homologous recombination (HR) repair, facilitating tumor cells to escape platinum-induced apoptotic pressure. In addition, SU056, an inhibitor targeting the YBX1 protein, demonstrated the potential to reverse platinum resistance in subcutaneous and PDO orthotopic xenograft models. In conclusion, our study suggested that YBX1 promoted the development of platinum resistance in ovarian cancer by recognizing m5C modifications, might be a potential target for reversing drug-resistant therapy. |
| 样品范围 |
Multiisolate |
| 发布日期 |
2025-05-09 |
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Natural Science Foundation of China (NSFC)
|
|
81872119
|
|
|
|
| 提交者 |
Wenjun
cheng (chengwenjun@jsph.org.cn)
|
| 提交单位 |
The First Affiliated Hospital of Nanjing Medical University |
| 提交日期 |
2023-05-09 |
