| First Author | Beckers A | Year | 2015 |
| Journal | Cancer Lett | Volume | 366 |
| Issue | 1 | Pages | 123-32 |
| PubMed ID | 26123663 | Mgi Jnum | J:222998 |
| Mgi Id | MGI:5646315 | Doi | 10.1016/j.canlet.2015.06.015 |
| Citation | Beckers A, et al. (2015) MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma. Cancer Lett 366(1):123-32 |
| abstractText | 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. |
