RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation
Abstract Neuroblastoma (NB) is a kind of typical life-threatening extracranial tumor in children. N6-methyladenosine (m6A) modification is closely related to multiple cancer pathological processes. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a top-ranked prognostic risk gene in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-05-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01449-3 |
| _version_ | 1797827718912409600 |
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| author | Kai Zhu Tingting Gao Zhiru Wang Liaoran Zhang Kezhe Tan Zhibao Lv |
| author_facet | Kai Zhu Tingting Gao Zhiru Wang Liaoran Zhang Kezhe Tan Zhibao Lv |
| author_sort | Kai Zhu |
| collection | DOAJ |
| description | Abstract Neuroblastoma (NB) is a kind of typical life-threatening extracranial tumor in children. N6-methyladenosine (m6A) modification is closely related to multiple cancer pathological processes. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a top-ranked prognostic risk gene in NB; however, its function is uncertain. The expression of m6A-associated enzymes in patients with NB was analyzed using the Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The IGF2BP3 level in NB cell lines and primary samples was tested using quantitative real-time polymerase chain reaction (qRT-PCR), western blot method, and immunohistochemical analysis. The IGF2BP3 function in cell proliferation was clarified based on many functional in vitro and in vivo experiments. The interaction between IGF2BP3 and N-myc was researched via RNA immunoprecipitation (RIP), m6A RNA immunoprecipitation (MeRIP), and chromatin immunoprecipitation (ChIP) assays. The 16 m6A-regulated enzymes in NB were researched, and the result indicated that IGF2BP3 overexpression was related to cancer progression, COG risk, and survival based on the GEO and TARGET databases. Besides, the IGF2BP3 and MYCN levels were positively correlated. IGF2BP3 expression levels increased in MYCN-amplified NB clinical samples and cells. Knockdown of IGF2BP3 inhibited N-myc expression and NB cell proliferation in vitro and in vivo. IGF2BP3 regulates MYCN RNA stability by modifying m6A. In addition, we demonstrated that N-myc is a transcription factor that directly promotes IGF2BP3 expression in NB cells. IGF2BP3 regulates the proliferation of NB cells via m6A modification of MYCN. N-myc also acts as a transcription factor that regulates IGF2BP3 expression. A positive feedback loop between IGF2BP3 and N-myc facilitates NB cell proliferation. |
| first_indexed | 2024-04-09T12:52:52Z |
| format | Article |
| id | doaj.art-8d20d1a4240c45148cb4a20b28ca3d99 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-09T12:52:52Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-8d20d1a4240c45148cb4a20b28ca3d992023-05-14T11:08:18ZengNature Publishing GroupCell Death Discovery2058-77162023-05-019111010.1038/s41420-023-01449-3RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferationKai Zhu0Tingting Gao1Zhiru Wang2Liaoran Zhang3Kezhe Tan4Zhibao Lv5Department of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Neuroblastoma (NB) is a kind of typical life-threatening extracranial tumor in children. N6-methyladenosine (m6A) modification is closely related to multiple cancer pathological processes. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a top-ranked prognostic risk gene in NB; however, its function is uncertain. The expression of m6A-associated enzymes in patients with NB was analyzed using the Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The IGF2BP3 level in NB cell lines and primary samples was tested using quantitative real-time polymerase chain reaction (qRT-PCR), western blot method, and immunohistochemical analysis. The IGF2BP3 function in cell proliferation was clarified based on many functional in vitro and in vivo experiments. The interaction between IGF2BP3 and N-myc was researched via RNA immunoprecipitation (RIP), m6A RNA immunoprecipitation (MeRIP), and chromatin immunoprecipitation (ChIP) assays. The 16 m6A-regulated enzymes in NB were researched, and the result indicated that IGF2BP3 overexpression was related to cancer progression, COG risk, and survival based on the GEO and TARGET databases. Besides, the IGF2BP3 and MYCN levels were positively correlated. IGF2BP3 expression levels increased in MYCN-amplified NB clinical samples and cells. Knockdown of IGF2BP3 inhibited N-myc expression and NB cell proliferation in vitro and in vivo. IGF2BP3 regulates MYCN RNA stability by modifying m6A. In addition, we demonstrated that N-myc is a transcription factor that directly promotes IGF2BP3 expression in NB cells. IGF2BP3 regulates the proliferation of NB cells via m6A modification of MYCN. N-myc also acts as a transcription factor that regulates IGF2BP3 expression. A positive feedback loop between IGF2BP3 and N-myc facilitates NB cell proliferation.https://doi.org/10.1038/s41420-023-01449-3 |
| spellingShingle | Kai Zhu Tingting Gao Zhiru Wang Liaoran Zhang Kezhe Tan Zhibao Lv RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation Cell Death Discovery |
| title | RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation |
| title_full | RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation |
| title_fullStr | RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation |
| title_full_unstemmed | RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation |
| title_short | RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation |
| title_sort | rna n6 methyladenosine reader igf2bp3 interacts with mycn and facilitates neuroblastoma cell proliferation |
| url | https://doi.org/10.1038/s41420-023-01449-3 |
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