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Expression of retinoic acid receptor gamma is modulated by miR-30a

Barrett, A, Shi, J-Y, Howell, L, Sbirkov, Y, Brown, G, Zelent, A and Petrie, Kevin (2023) Expression of retinoic acid receptor gamma is modulated by miR-30a. Klinische Pädiatrie, 235 (3). p. 191. ISSN 0300-8630

Item Type: Article

Abstract

All-trans-retinoic acid (ATRA) plays critical regulatory roles in normal haematopoiesis and the pathogenesis of adult and pediatric acute myeloid leukemia (AML). While ATRA can inhibit growth and stimulates myeloid differentiation via RARα, it is equally potent in causing expansion of haematopoietic stem cells via RARγ. RARG mRNA is expressed in AML patients and normal stem/progenitor cells but not in more mature myeloid cells. Changes in RARγ expression are paralleled by a reciprocal change in expression of RARG 3’-targeting miRNAs (mIR-24, mIR-30a, mIR-331). RARγ protein and RARG mRNA are also expressed in cell lines derived from primary AML samples but not in ATRA-responsive AML cell lines. Lastly, expression of mIR-30a in TEX cells promotes differentiation and inhibits proliferation. Our results suggest that miRNA-mediated down-regulation of RARγ expression in the myeloid lineage switches ATRA responsiveness from RARγ-mediated pro-proliferation to RARα-mediated pro-differentiation and that the combinatorial use of RARα and RARγ selective agonists and antagonists, respectively, could be effective in retinoid-based differentiation therapy of AML.

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Depositing User: Kevin Petrie

Identifiers

Item ID: 17352
Identification Number: https://doi.org/10.1055/s-0043-1768498
ISSN: 0300-8630
URI: http://sure.sunderland.ac.uk/id/eprint/17352
Official URL: http://dx.doi.org/10.1055/s-0043-1768498

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 27 Feb 2024 09:21
Last Modified: 27 Feb 2024 09:21

Contributors

Author: Kevin Petrie ORCID iD
Author: A Barrett
Author: J-Y Shi
Author: L Howell
Author: Y Sbirkov
Author: G Brown
Author: A Zelent

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences

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