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- Title
Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia.
- Authors
Kogut, Sophie; Paculova, Hana; Rodriguez, Princess; Boyd, Joseph; Richman, Alyssa; Palaria, Amrita; Schjerven, Hilde; Frietze, Seth
- Abstract
The hematopoietic transcription factor Ikaros (IKZF1) regulates normal B cell development and functions as a tumor suppressor in precursor B cell acute lymphoblastic leukemia (B-ALL). MicroRNAs (miRNAs) are small regulatory RNAs that through post-transcriptional gene regulation play critical roles in intracellular processes including cell growth in cancer. However, the role of Ikaros in the regulation of miRNA expression in developing B cells is unknown. In this study, we examined the Ikaros-regulated miRNA targets using human IKZF1-mutated Ph+ B-ALL cell lines. Inducible expression of wild-type Ikaros (the Ik1 isoform) caused B-ALL growth arrest and exit from the cell cycle. Global miRNA expression analysis revealed a total of 31 miRNAs regulated by IK1, and ChIP-seq analysis showed that Ikaros bound to several Ik1-responsive miRNA genes. Examination of the prognostic significance of miRNA expression in B-ALL indicate that the IK1-regulated miRNAs hsa-miR-26b, hsa-miR-130b and hsa-miR-4649 are significantly associated with outcome in B-ALL. Our findings establish a potential regulatory circuit between the tumor-suppressor Ikaros and the oncogenic miRNA networks in IKZF1-mutated B-ALL. These results indicate that Ikaros regulates the expression of a subset of miRNAs, of which several may contribute to B-ALL growth.
- Subjects
LYMPHOBLASTIC leukemia; GENE expression; ACUTE leukemia; NON-coding RNA; GENETIC regulation
- Publication
Epigenomes, 2022, Vol 6, Issue 4, p37
- ISSN
2075-4655
- Publication type
Article
- DOI
10.3390/epigenomes6040037