Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia

Sophie Kogut
,
Hana Paculova
ORCID logo ,
Princess Rodriguez
,
Joseph Boyd
,
Alyssa Richman
,
Amrita Palaria
,
Hilde Schjerven
* ,
Seth Frietze
* ORCID logo
Version 1 : Received: 15 August 2022 / Approved: 17 August 2022 / Online: 17 August 2022 (11:29:02 CEST)

How to cite: Kogut, S.; Paculova, H.; Rodriguez, P.; Boyd, J.; Richman, A.; Palaria, A.; Schjerven, H.; Frietze, S. Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia. Preprints 2022, 2022080323. https://doi.org/10.20944/preprints202208.0323.v1 Kogut, S.; Paculova, H.; Rodriguez, P.; Boyd, J.; Richman, A.; Palaria, A.; Schjerven, H.; Frietze, S. Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia. Preprints 2022, 2022080323. https://doi.org/10.20944/preprints202208.0323.v1

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 patient-derived IKZF1-mutated B-ALL xenograft-derived 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.

Keywords

miRNA; IKZF1; Acute Lymphoblastic Leukemia

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.