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@article{1354167,
author = {Kopparapu, Pradeep Kumar and Bhoi, Sujata and Mansouri, Larry and Arabanian, Laleh S. and Plevová, Karla and Pospíšilová, Šárka and Wasik, Agata M. and Croci, Giorgio Alberto and Sander, Brigitta and Paulli, Marco and Rosenquist, Richard and Kanduri, Meena},
article_location = {Philadelphia},
article_number = {5},
doi = {http://dx.doi.org/10.1080/15592294.2016.1164375},
keywords = {Chronic lymphocytic leukemia; DNA methylation; mantle cell lymphoma; microRNA; tumor suppressor},
language = {eng},
issn = {1559-2294},
journal = {Epigenetics},
title = {Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression},
url = {http://www.tandfonline.com/doi/full/10.1080/15592294.2016.1164375?scroll=top&needAccess=true},
volume = {11},
year = {2016}
}
TY - JOUR
ID - 1354167
AU - Kopparapu, Pradeep Kumar - Bhoi, Sujata - Mansouri, Larry - Arabanian, Laleh S. - Plevová, Karla - Pospíšilová, Šárka - Wasik, Agata M. - Croci, Giorgio Alberto - Sander, Brigitta - Paulli, Marco - Rosenquist, Richard - Kanduri, Meena
PY - 2016
TI - Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression
JF - Epigenetics
VL - 11
IS - 5
SP - 335-343
EP - 335-343
PB - TAYLOR & FRANCIS INC
SN - 15592294
KW - Chronic lymphocytic leukemia
KW - DNA methylation
KW - mantle cell lymphoma
KW - microRNA
KW - tumor suppressor
UR - http://www.tandfonline.com/doi/full/10.1080/15592294.2016.1164375?scroll=top&needAccess=true
L2 - http://www.tandfonline.com/doi/full/10.1080/15592294.2016.1164375?scroll=top&needAccess=true
N2 - Downregulation of miR26A1 has been reported in various B-cell malignancies; however, the mechanism behind its deregulation remains largely unknown. We investigated miR26A1 methylation and expression levels in a well-characterized series of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). From 450K methylation arrays, we first observed miR26A1 (cg26054057) as uniformly hypermethylated in MCL (n = 24) (all >75%), while CLL (n = 18) showed differential methylation between prognostic subgroups. Extended analysis using pyrosequencing confirmed our findings and real-time quantitative PCR verified low miR26A1 expression in both CLL (n = 70) and MCL (n = 38) compared to normal B-cells. Notably, the level of miR26A1 methylation predicted outcome in CLL, with higher levels seen in poor-prognostic, IGHV-unmutated CLL. Since EZH2 was recently reported as a target for miR26A1, we analyzed the expression levels of both miR26A1 and EZH2 in primary CLL samples and observed an inverse correlation. By overexpression of miR26A1 in CLL and MCL cell lines, reduced EZH2 protein levels were observed using both Western blot and flow cytometry. In contrast, methyl-inhibitor treatment led to upregulated miR26A1 expression with a parallel decrease of EZH2 expression. Finally, increased levels of apoptosis were observed in miR26A1-overexpressing cell lines, further underscoring the functional relevance of miR26A1. In summary, we propose that epigenetic silencing of miR26A1 is required for the maintenance of increased levels of EZH2, which in turn translate into a worse outcome, as shown in CLL, highlighting miR26A1 as a tumor suppressor miRNA.
ER -
KOPPARAPU, Pradeep Kumar, Sujata BHOI, Larry MANSOURI, Laleh S. ARABANIAN, Karla PLEVOVÁ, Šárka POSPÍŠILOVÁ, Agata M. WASIK, Giorgio Alberto CROCI, Brigitta SANDER, Marco PAULLI, Richard ROSENQUIST and Meena KANDURI. Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression. \textit{Epigenetics}. Philadelphia: TAYLOR \&{} FRANCIS INC, 2016, vol.~11, No~5, p.~335-343. ISSN~1559-2294. Available from: https://dx.doi.org/10.1080/15592294.2016.1164375.
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