MicroRNA-128-3p is a novel oncomiR targeting PHF6 in T-cell acute lymphoblastic leukemia Journal Article
| Authors: | Mets, E.; Van Peer, G.; Van Der Meulen, J.; Boice, M.; Taghon, T.; Goossens, S.; Mestdagh, P.; Benoit, Y.; De Moerloose, B.; Van Roy, N.; Poppe, B.; Vandesompele, J.; Wendel, H. G.; Van Vlierberghe, P.; Speleman, F.; Rondou, P. |
| Article Title: | MicroRNA-128-3p is a novel oncomiR targeting PHF6 in T-cell acute lymphoblastic leukemia |
| Abstract: | T-cell acute lymphoblastic leukemia arises from the leukemic transformation of developing thymocytes and results from cooperative genetic lesions. Inactivation of the PHF6 gene is frequently observed in T-cell acute lymphoblastic leukemia, suggesting an important tumor suppressive role for PHF6 in the pathobiology of this leukemia. Although the precise function of PHF6 is still unknown, this gene is most likely involved in chromatin regulation, a strongly emerging theme in T-cell acute lymphoblastic leukemia. In this context, our previous description of a cooperative microRNA regulatory network controlling several well-known T-cell acute lymphoblastic leukemia tumor suppressor genes, including PHF6, is of great importance. Given the high frequency of PHF6 lesions in T-cell acute lymphoblastic leukemia and the integration of PHF6 in this microRNA regulatory network, we aimed to identify novel oncogenic microRNAs in T-cell acute lymphoblastic leukemia which suppress PHF6. To this end, we performed an unbiased PHF6 3'UTR-microRNA library screen and combined the results with microRNA profiling data of samples from patients with T-cell acute lymphoblastic leukemia and normal thymocyte subsets. We selected miR-128-3p as a candidate PHF6-targeting, oncogenic microRNA and demonstrated regulation of PHF6 expression upon modulation of this microRNA in T-cell acute lymphoblastic leukemia cell lines. In vivo evidence of an oncogenic role of this microRNA in T-cell acute lymphoblastic leukemia was obtained through accelerated leukemia onset in a NOTCH1-induced T-cell acute lymphoblastic leukemia mouse model upon miR-128-3p over-expression. We conclude that miR-128-3p is a strong novel candidate oncogenic microRNA in T-cell acute lymphoblastic leukemia which targets the PHF6 tumor suppressor gene. © 2014 Ferrata Storti Foundation. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; nonhuman; genetic analysis; animal cell; mouse; gene; microrna; gene expression; luciferase; animal model; histology; acute lymphoblastic leukemia; cancer inhibition; genetic transfection; messenger rna; gene interaction; western blotting; down regulation; real time polymerase chain reaction; computer model; site directed mutagenesis; microrna 26a; notch1 receptor; firefly; phf6 gene; microrna 20a; human; article; microrna 128 3p; gene regulatoy network; luciferase assay |
| Journal Title: | Haematologica |
| Volume: | 99 |
| Issue: | 8 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 2014-08-01 |
| Start Page: | 1326 |
| End Page: | 1333 |
| Language: | English |
| DOI: | 10.3324/haematol.2013.099515 |
| PROVIDER: | scopus |
| PMCID: | PMC4116831 |
| PUBMED: | 24895337 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2014 -- CODEN: HAEMA -- Source: Scopus |
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