RUNX3 overexpression inhibits normal human erythroid development

Menezes, Ana Catarina, Dixon, Christabel, Scholz, Anna, Nicholson, Rachael, Leckenby, Adam, Azevedo, Aleksandra, Baker, Sarah ORCID: https://orcid.org/0000-0002-7474-9757, Gilkes, Amanda F., Davies, Sara, Darley, Richard L. ORCID: https://orcid.org/0000-0003-0879-0724 and Tonks, Alex ORCID: https://orcid.org/0000-0002-6073-4976 2022. RUNX3 overexpression inhibits normal human erythroid development. Scientific Reports 12 , 1243. 10.1038/s41598-022-05371-z

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Abstract

RUNX proteins belong to a family of transcription factors essential for cellular proliferation, differentiation, and apoptosis with emerging data implicating RUNX3 in haematopoiesis and haematological malignancies. Here we show that RUNX3 plays an important regulatory role in normal human erythropoiesis. The impact of altering RUNX3 expression on erythropoiesis was determined by transducing human CD34+ cells with RUNX3 overexpression or shRNA knockdown vectors. Analysis of RUNX3 mRNA expression showed that RUNX3 levels decreased during erythropoiesis. Functionally, RUNX3 overexpression had a modest impact on early erythroid growth and development. However, in late-stage erythroid development, RUNX3 promoted growth and inhibited terminal differentiation with RUNX3 overexpressing cells exhibiting lower expression of glycophorin A, greater cell size and less differentiated morphology. These results suggest that suppression of RUNX3 is required for normal erythropoiesis. Overexpression of RUNX3 increased colony formation in liquid culture whilst, corresponding RUNX3 knockdown suppressed colony formation but otherwise had little impact. This study demonstrates that the downregulation of RUNX3 observed in normal human erythropoiesis is important in promoting the terminal stages of erythroid development and may further our understanding of the role of this transcription factor in haematological malignancies.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Nature Research
ISSN:	2045-2322
Funders:	Cancer Research UK
Date of First Compliant Deposit:	14 January 2022
Date of Acceptance:	11 January 2022
Last Modified:	06 Nov 2024 22:47
URI:	https://orca.cardiff.ac.uk/id/eprint/146704

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