SAP30, a novel autophagy regulatory gene in neuroblastoma
Neuroblastoma (NB), a devastating pediatric cancer originating from neural crest cells crucial for nervous system development, poses a significant therapeutic challenge. Despite chemotherapy being the primary treatment, approximately 70% of high-risk NB cases develop resistance. Autophagy is vital f...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924001589 |
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| author | Anup S. Pathania Anjana Murugan Areem Zahid Haritha Chava Don W. Coulter George A. Calin Kishore B. Challagundla |
| author_facet | Anup S. Pathania Anjana Murugan Areem Zahid Haritha Chava Don W. Coulter George A. Calin Kishore B. Challagundla |
| author_sort | Anup S. Pathania |
| collection | DOAJ |
| description | Neuroblastoma (NB), a devastating pediatric cancer originating from neural crest cells crucial for nervous system development, poses a significant therapeutic challenge. Despite chemotherapy being the primary treatment, approximately 70% of high-risk NB cases develop resistance. Autophagy is vital for neuronal development, balance, and differentiation of neural stem cells into mature neurons. However, the intricate mechanisms governing autophagy and the pivotal genes orchestrating its regulation in NB remain largely elusive. In this study, we first identified Sin3A Associated Protein 30 (SAP30) as a novel regulator of autophagy in NB. Silencing SAP30 inhibits autophagy and disrupts starvation-induced physiological autophagy in NB cells. Conversely, ectopic expression of SAP30 induces autophagy in NB cells under normal or starvation conditions. Mechanistically, SAP30 transcriptionally regulates STX17, a crucial protein involved in autophagosome-lysosome fusion during autophagy. Reduction of SAP30 decreases STX17 expression, hindering its translocation to the autophagic membrane and inhibiting autophagosome-lysosome fusion. SAP30-mediated autophagy enhances cell growth and provides protection in NB cells treated with chemotherapy drugs. Notably, suppressing SAP30 in vivo increases LC3B accumulation, an autophagy marker, along with reduced proliferation markers, both in vivo and in PDX tumors. Therefore, SAP30 emerges as a potential target to enhance NB responsiveness to chemotherapy drugs. |
| format | Article |
| id | doaj-art-09aa21a402f1411d812149b9d81fa5f1 |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-09aa21a402f1411d812149b9d81fa5f12025-01-11T06:42:25ZengElsevierMolecular Therapy: Oncology2950-32992025-03-01331200916SAP30, a novel autophagy regulatory gene in neuroblastomaAnup S. Pathania0Anjana Murugan1Areem Zahid2Haritha Chava3Don W. Coulter4George A. Calin5Kishore B. Challagundla6The Child Health Research Institute, Department of Biochemistry and Molecular Biology, and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USAUNMC High School Alliance, Department of Biochemistry and Molecular Biology, and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USAUNMC High School Alliance, Department of Biochemistry and Molecular Biology, and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pediatrics, Division of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE 68198, USATranslational Molecular Pathology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The RNA Interference and Non-coding RNA Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USAThe Child Health Research Institute, Department of Biochemistry and Molecular Biology, and the Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine, Middletown, NY 10940, USA; Corresponding author: Kishore B. Challagundla, Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine, Middletown, NY 10940, USANeuroblastoma (NB), a devastating pediatric cancer originating from neural crest cells crucial for nervous system development, poses a significant therapeutic challenge. Despite chemotherapy being the primary treatment, approximately 70% of high-risk NB cases develop resistance. Autophagy is vital for neuronal development, balance, and differentiation of neural stem cells into mature neurons. However, the intricate mechanisms governing autophagy and the pivotal genes orchestrating its regulation in NB remain largely elusive. In this study, we first identified Sin3A Associated Protein 30 (SAP30) as a novel regulator of autophagy in NB. Silencing SAP30 inhibits autophagy and disrupts starvation-induced physiological autophagy in NB cells. Conversely, ectopic expression of SAP30 induces autophagy in NB cells under normal or starvation conditions. Mechanistically, SAP30 transcriptionally regulates STX17, a crucial protein involved in autophagosome-lysosome fusion during autophagy. Reduction of SAP30 decreases STX17 expression, hindering its translocation to the autophagic membrane and inhibiting autophagosome-lysosome fusion. SAP30-mediated autophagy enhances cell growth and provides protection in NB cells treated with chemotherapy drugs. Notably, suppressing SAP30 in vivo increases LC3B accumulation, an autophagy marker, along with reduced proliferation markers, both in vivo and in PDX tumors. Therefore, SAP30 emerges as a potential target to enhance NB responsiveness to chemotherapy drugs.http://www.sciencedirect.com/science/article/pii/S2950329924001589MT: Novel therapeutic targets and biomarker development special issueneuroblastomaautophagySAP30autophagosomechemotherapy response |
| spellingShingle | Anup S. Pathania Anjana Murugan Areem Zahid Haritha Chava Don W. Coulter George A. Calin Kishore B. Challagundla SAP30, a novel autophagy regulatory gene in neuroblastoma Molecular Therapy: Oncology MT: Novel therapeutic targets and biomarker development special issue neuroblastoma autophagy SAP30 autophagosome chemotherapy response |
| title | SAP30, a novel autophagy regulatory gene in neuroblastoma |
| title_full | SAP30, a novel autophagy regulatory gene in neuroblastoma |
| title_fullStr | SAP30, a novel autophagy regulatory gene in neuroblastoma |
| title_full_unstemmed | SAP30, a novel autophagy regulatory gene in neuroblastoma |
| title_short | SAP30, a novel autophagy regulatory gene in neuroblastoma |
| title_sort | sap30 a novel autophagy regulatory gene in neuroblastoma |
| topic | MT: Novel therapeutic targets and biomarker development special issue neuroblastoma autophagy SAP30 autophagosome chemotherapy response |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924001589 |
| work_keys_str_mv | AT anupspathania sap30anovelautophagyregulatorygeneinneuroblastoma AT anjanamurugan sap30anovelautophagyregulatorygeneinneuroblastoma AT areemzahid sap30anovelautophagyregulatorygeneinneuroblastoma AT harithachava sap30anovelautophagyregulatorygeneinneuroblastoma AT donwcoulter sap30anovelautophagyregulatorygeneinneuroblastoma AT georgeacalin sap30anovelautophagyregulatorygeneinneuroblastoma AT kishorebchallagundla sap30anovelautophagyregulatorygeneinneuroblastoma |