HMGA1 negatively regulates NUMB expression at transcriptional and post transcriptional level in glioblastoma stem cells
| العنوان: | HMGA1 negatively regulates NUMB expression at transcriptional and post transcriptional level in glioblastoma stem cells |
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| المؤلفون: | Yalçın Kuzay, Alfredo Fusco, Teresa Savarese, Anna Pepe, Antonella Federico, Nadia Tosti, Francesca Puca, Marianna Colamaio, Sabrina Battista, Daniela Sarnataro, Federica D'Alessio, Sonia Morlando, Marco De Martino, Sihana Ziberi |
| المساهمون: | Puca, F., Tosti, N., Federico, A., Kuzay, Y., Pepe, A., Morlando, S., Savarese, T., D'Alessio, F., Colamaio, M., Sarnataro, D., Ziberi, S., De Martino, M., Fusco, A., Battista, S. |
| المصدر: | Cell Cycle Cell cycle (Georget. Tex.) 18 (2019): 1446–1457. doi:10.1080/15384101.2019.1618541 info:cnr-pdr/source/autori:Puca F.; Tosti N.; Federico A.; Kuzay Y.; Pepe A.; Morlando S.; Savarese T.; D'Alessio F.; Colamaio M.; Sarnataro D.; Ziberi S.; De Martino M.; Fusco A.; Battista S./titolo:HMGA1 negatively regulates NUMB expression at transcriptional and post transcriptional level in glioblastoma stem cells/doi:10.1080%2F15384101.2019.1618541/rivista:Cell cycle (Georget. Tex.)/anno:2019/pagina_da:1446/pagina_a:1457/intervallo_pagine:1446–1457/volume:18 |
| بيانات النشر: | Informa UK Limited, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, cancer stem cell, HMGA1, Transcription, Genetic, Down-Regulation, Nerve Tissue Proteins, [object Object], Biology, Cell Line, 03 medical and health sciences, 0302 clinical medicine, NOTCH1, NUMB, Downregulation and upregulation, Cancer stem cell, Cell Line, Tumor, Humans, Gene silencing, HMGA1a Protein, RNA Processing, Post-Transcriptional, Promoter Regions, Genetic, Molecular Biology, Transcription factor, Brain Neoplasms, Multipotent Stem Cells, Brain, Membrane Proteins, Cell Biology, asymmetric division, Neural stem cell, Cell biology, MicroRNAs, HEK293 Cells, 030104 developmental biology, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, biology.protein, Stem cell, Glioblastoma, Cell Division, Research Paper, Developmental Biology |
| الوصف: | Glioblastoma (GBM) is a lethal, fast-growing brain cancer, affecting 2-3 per 100,000 adults per year. It arises from multipotent neural stem cells which have reduced their ability to divide asymmetrically and hence divide symmetrically, generating increasing number of cancer stem cells, fostering tumor growth. We have previously demonstrated that the architectural transcription factor HMGA1 is highly expressed in brain tumor stem cells (BTSCs) and that its silencing increases stem cell quiescence, reduces self-renewal and sphere-forming efficiency in serial passages, suggesting a shift from symmetric to asymmetric division. Since NUMB expression is fundamental for the fulfillment of asymmetric division in stem cells, and is lost or reduced in many tumors, including GBM, we have investigated the ability of HMGA1 to regulate NUMB expression. Here, we show that HMGA1 negatively regulates NUMB expression at transcriptional level, by binding its promoter and counteracting c/EBP-? and at posttranscriptional level, by regulating the expression of MSI1 and of miR-146a. Finally, we report that HMGA1 knockdown-induced NUMB upregulation leads to the downregulation of the NOTCH1 pathway. Therefore, the data reported here indicate that HMGA1 negatively regulates NUMB expression in BTSCs, further supporting HMGA1 targeting as innovative and effective anti-cancer therapy. |
| تدمد: | 1551-4005 1538-4101 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::252acc5b1c4e0f19a1fc424f381dcfa0 https://doi.org/10.1080/15384101.2019.1618541 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....252acc5b1c4e0f19a1fc424f381dcfa0 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 15514005 15384101 |
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