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MicroRNA-124 regulates glucocorticoid sensitivity by targeting phosphodiesterase 4B in diffuse large B cell lymphoma

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Author(s)
Jinyoung KimDawoom JeongJehyun NamThazin Nwe AungJeong-An GimKeon Uk ParkSang-Woo Kim
Keimyung Author(s)
Park, Keon Uk
Department
Dept. of Internal Medicine (내과학)
Journal Title
Gene
Issued Date
2015
Volume
558
Issue
1
Abstract
Glucocorticoids (GCs) are chemotherapeutic drugs commonly used to treat hematological malignancies. However,
a significant fraction of patients develop resistance to GCs during treatment. A better insight into how GC resistance
develops is therefore needed. It was previously shown that cyclic AMP (cAMP) induces sensitivity to GCs
by inhibiting the AKT/mTOR/MCL1 signaling, while high levels of phosphodiesterase 4B (PDE4B) reverse the effect
of cAMP on GC responses in B-cell lymphoma. Here,we showthatmiR-124 influences GC-induced apoptosis
by directly targeting PDE4B. Stable expression ofmiR-124 in diffuse large B cell lymphoma (DLBCL) cell lines diminished
PDE4B expression. This was associated with increased cAMP levels, inhibition of the AKT/mTOR/MCL1
survival pathway, upregulation of GRα expression, and improved sensitivity to GCs in the presence of forskolin,
an activator of adenylyl cyclase. Interestingly, miR-124 did not affect GC sensitivity in the absence of forskolin,
indicating that the effect of thismiRNA is accomplished via downregulation of PDE4B expression. Further, restoration
of PDE4B expression inmiR-124 cells rescued the phenotypic effect of thismiRNA, demonstrating the critical
role of PDE4B in miR-124-mediated regulation of the GC response. Our study supports the notion that miR-
124 could be an attractive therapeutic target for overcoming GC resistance in DLBCL.
Keimyung Author(s)(Kor)
박건욱
Publisher
School of Medicine
Citation
Jinyoung Kim et al. (2015). MicroRNA-124 regulates glucocorticoid sensitivity by targeting
phosphodiesterase 4B in diffuse large B cell lymphoma. Gene, 558(1), 173–180. doi: 10.1016/j.gene.2015.01.001
Type
Article
ISSN
0378-1119
Source
https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(15)00002-5
DOI
10.1016/j.gene.2015.01.001
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35768
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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