| Autor: |
Philip Prathipati, Anup S. Pathania, Nagendra K. Chaturvedi, Subash C. Gupta, Siddappa N. Byrareddy, Don W. Coulter, Kishore B. Challagundla |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 35, Iss 2, Pp 101543- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1016/j.omtn.2022.03.014 |
| Popis: |
Neuroblastoma is the most devastating extracranial solid malignancy in children. Despite an intense treatment regimen, the prognosis for high-risk neuroblastoma patients remains poor, with less than 40% survival. So far, MYCN amplification status is considered the most prognostic factor but corresponds to only ∼25% of neuroblastoma patients. Therefore, it is essential to identify a better prognosis and therapy response marker in neuroblastoma patients. We applied robust bioinformatic data mining tools, such as weighted gene co-expression network analysis, cisTarget, and single-cell regulatory network inference and clustering on two neuroblastoma patient datasets. We found Sin3A-associated protein 30 (SAP30), a driver transcription factor positively associated with high-risk, progression, stage 4, and poor survival in neuroblastoma patient cohorts. Tumors of high-risk neuroblastoma patients and relapse-specific patient-derived xenografts showed higher SAP30 levels. The advanced pharmacogenomic analysis and CRISPR-Cas9 screens indicated that SAP30 essentiality is associated with cisplatin resistance and further showed higher levels in cisplatin-resistant patient-derived xenograft tumor cell lines. Silencing of SAP30 induced cell death in vitro and led to a reduced tumor burden and size in vivo. Altogether, these results indicate that SAP30 is a better prognostic and cisplatin-resistance marker and thus a potential drug target in high-risk neuroblastoma. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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