PNMA1 mediates melphalam chemoresistance in retinoblastoma via promoting DNA repair
Abstract Retinoblastoma (RB) is the most common malignant eye tumor in children. Cytotoxic drugs like melphalam often cause significant side effects and acquired resistance in RB treatment. Here, the impact of Paraneoplastic Ma1 (PNMA1) on RB progression and chemotherapy resistance was investigated....
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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: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-12206-0 |
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| Summary: | Abstract Retinoblastoma (RB) is the most common malignant eye tumor in children. Cytotoxic drugs like melphalam often cause significant side effects and acquired resistance in RB treatment. Here, the impact of Paraneoplastic Ma1 (PNMA1) on RB progression and chemotherapy resistance was investigated. A series of bioinformatics methods were used for differential expression genes and drug resistance genes screening. Western blot was performed for the detection of genes expression. CCK-8 and EdU staining were assessed for cell viability. Clone formation and TUNEL staining were examined for cell viability and apoptosis. Wound healing and transwell assays were analyzed for the cell migrated and invasive abilities. Immunofluorescence was observed for γ-H2AX expression. Colorimetric PARP/Apoptosis Assay was used for PARP activity. PNMA1 was upregulated in RB tumor tissues, and high expression of PNMA1 promotes RB cells’ chemoresistance to melphalam, while downregulation of PNMA1 reversed chemoresistance in resistant cells. Furthermore, the mechanism by which PNMA1 mediated chemoresistance to melphalam, discovered that PNMA1 might facilitate melphalam resistance through the c-myc-mediated DNA damage repair pathway. PNMA1 functions as a tumor-promoting factor in retinoblastoma and may regulate melphalam resistance through the upregulation of the c-myc gene and the involvement in DNA damage repair. |
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| ISSN: | 2045-2322 |