The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain.
Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we sh...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-05-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5453605?pdf=render |
| _version_ | 1818192396693798912 |
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| author | Yen-Chi Wu Kyu-Sun Lee Yan Song Stephan Gehrke Bingwei Lu |
| author_facet | Yen-Chi Wu Kyu-Sun Lee Yan Song Stephan Gehrke Bingwei Lu |
| author_sort | Yen-Chi Wu |
| collection | DOAJ |
| description | Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb. This feedback regulatory mechanism helps maintain the robustness of N signaling activity and NSC fate. Moreover, we show that a Numb-Myc axis mediates the effects of ban on nucleolar and cellular growth independently or downstream of N. Our results highlight intricate transcriptional as well as translational control mechanisms and feedback regulation in the N signaling network, with important implications for NSC biology and cancer biology. |
| first_indexed | 2024-12-12T00:29:50Z |
| format | Article |
| id | doaj.art-aa131f964d57428da6d13aa5974dd23d |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-12T00:29:50Z |
| publishDate | 2017-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-aa131f964d57428da6d13aa5974dd23d2022-12-22T00:44:31ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-05-01135e100678510.1371/journal.pgen.1006785The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain.Yen-Chi WuKyu-Sun LeeYan SongStephan GehrkeBingwei LuNotch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb. This feedback regulatory mechanism helps maintain the robustness of N signaling activity and NSC fate. Moreover, we show that a Numb-Myc axis mediates the effects of ban on nucleolar and cellular growth independently or downstream of N. Our results highlight intricate transcriptional as well as translational control mechanisms and feedback regulation in the N signaling network, with important implications for NSC biology and cancer biology.http://europepmc.org/articles/PMC5453605?pdf=render |
| spellingShingle | Yen-Chi Wu Kyu-Sun Lee Yan Song Stephan Gehrke Bingwei Lu The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain. PLoS Genetics |
| title | The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain. |
| title_full | The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain. |
| title_fullStr | The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain. |
| title_full_unstemmed | The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain. |
| title_short | The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain. |
| title_sort | bantam microrna acts through numb to exert cell growth control and feedback regulation of notch in tumor forming stem cells in the drosophila brain |
| url | http://europepmc.org/articles/PMC5453605?pdf=render |
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