MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma
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| Title: | MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma |
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| Authors: | Johannes H. Schulte, Frank Speleman, Saurabh Agarwal, Moritz Gartlgruber, Belamy B. Cheung, Jan J. Molenaar, Gert Van Peer, Glenn M. Marshall, Daniel R. Carter, Kristina Althoff, Jo Vandesompele, Anneleen Beckers, Hetty Helsmoortel, Katleen De Preter, Frank Westermann, Carl Herrmann, Jason M. Shohet, Yves Benoit |
| Source: | Cancer Letters |
| Publisher Information: | Elsevier BV, 2015. |
| Publication Year: | 2015 |
| Subject Terms: | Oncogene Proteins, 0301 basic medicine, N-Myc Proto-Oncogene Protein, 0303 health sciences, Tumor, Nuclear Proteins/physiology, Oncogene Proteins/physiology, Transcription, Genetic, Neuroblastoma/pathology, Medizin, Nuclear Proteins, RNA-Binding Proteins, RNA-Binding Proteins/genetics, Cell Line, 3. Good health, MicroRNAs/genetics, MicroRNAs, Neuroblastoma, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Humans, Transcription |
| Description: | LIN28B has been identified as an oncogene in various tumor entities, including neuroblastoma, a childhood cancer that originates from neural crest-derived cells, and is characterized by amplification of the MYCN oncogene. Recently, elevated LIN28B expression levels were shown to contribute to neuroblastoma tumorigenesis via let-7 dependent de-repression of MYCN. However, additional insight in the regulation of LIN28B in neuroblastoma is lacking. Therefore, we have performed a comprehensive analysis of the regulation of LIN28B in neuroblastoma, with a specific focus on the contribution of miRNAs. We show that MYCN regulates LIN28B expression in neuroblastoma tumors via two distinct parallel mechanisms. First, through an unbiased LIN28B-3'UTR reporter screen, we found that miR-26a-5p and miR-26b-5p regulate LIN28B expression. Next, we demonstrated that MYCN indirectly affects the expression of miR-26a-5p, and hence regulates LIN28B, therefore establishing an MYCN-miR-26a-5p-LIN28B regulatory axis. Second, we provide evidence that MYCN regulates LIN28B expression via interaction with the LIN28B promoter, establishing a direct MYCN-LIN28B regulatory axis. We believe that these findings mark LIN28B as an important effector of the MYCN oncogenic phenotype and underline the importance of MYCN-regulated miRNAs in establishing the MYCN-driven oncogenic process. |
| Document Type: | Article Other literature type |
| Language: | English |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2015.06.015 |
| Access URL: | https://europepmc.org/articles/pmc4837470?pdf=render https://pubmed.ncbi.nlm.nih.gov/26123663 https://research-portal.uu.nl/en/publications/360876d3-407e-4159-a908-80925d08a793 https://doi.org/10.1016/j.canlet.2015.06.015 https://researchinformation.amsterdamumc.org/en/publications/mycn-driven-regulatory-mechanisms-controlling-lin28b-in-neuroblas https://pubmed.ncbi.nlm.nih.gov/26123663/ https://biblio.ugent.be/publication/7040561 http://europepmc.org/articles/PMC4837470 https://core.ac.uk/display/141638526 https://www.sciencedirect.com/science/article/pii/S0304383515004085 http://europepmc.org/articles/pmc4837470 https://doi.org/10.1016/j.canlet.2015.06.015 |
| Rights: | Elsevier TDM |
| Accession Number: | edsair.doi.dedup.....342bc0101eea14de3a7b704f976907b4 |
| Database: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | LIN28B has been identified as an oncogene in various tumor entities, including neuroblastoma, a childhood cancer that originates from neural crest-derived cells, and is characterized by amplification of the MYCN oncogene. Recently, elevated LIN28B expression levels were shown to contribute to neuroblastoma tumorigenesis via let-7 dependent de-repression of MYCN. However, additional insight in the regulation of LIN28B in neuroblastoma is lacking. Therefore, we have performed a comprehensive analysis of the regulation of LIN28B in neuroblastoma, with a specific focus on the contribution of miRNAs. We show that MYCN regulates LIN28B expression in neuroblastoma tumors via two distinct parallel mechanisms. First, through an unbiased LIN28B-3'UTR reporter screen, we found that miR-26a-5p and miR-26b-5p regulate LIN28B expression. Next, we demonstrated that MYCN indirectly affects the expression of miR-26a-5p, and hence regulates LIN28B, therefore establishing an MYCN-miR-26a-5p-LIN28B regulatory axis. Second, we provide evidence that MYCN regulates LIN28B expression via interaction with the LIN28B promoter, establishing a direct MYCN-LIN28B regulatory axis. We believe that these findings mark LIN28B as an important effector of the MYCN oncogenic phenotype and underline the importance of MYCN-regulated miRNAs in establishing the MYCN-driven oncogenic process. |
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| ISSN: | 03043835 |
| DOI: | 10.1016/j.canlet.2015.06.015 |