Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899519 | Cancer Letters | 2015 | 10 Pages |
Abstract
We show that MYCN regulates LIN28B expression in neuroblastoma tumors via two distinct parallel mechanisms. First, through an unbiased LIN28B-3â²UTR 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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Authors
Anneleen Beckers, Gert Van Peer, Daniel R. Carter, Moritz Gartlgruber, Carl Herrmann, Saurabh Agarwal, Hetty H. Helsmoortel, Kristina Althoff, Jan J. Molenaar, Belamy B. Cheung, Johannes H. Schulte, Yves Benoit, Jason M. Shohet, Frank Westermann,