Epigenetic silencing of miR-26A1 in chronic lymphocytic
leukemia and mantle cell lymphoma: Impact on EZH2 expression

J 2016

Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression

KOPPARAPU, Pradeep Kumar, Sujata BHOI, Larry MANSOURI, Laleh S. ARABANIAN, Karla PLEVOVÁ et. al.

Basic information

Original name

Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression

Authors

KOPPARAPU, Pradeep Kumar (752 Sweden), Sujata BHOI (752 Sweden), Larry MANSOURI (752 Sweden), Laleh S. ARABANIAN (752 Sweden), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution), Agata M. WASIK (752 Sweden), Giorgio Alberto CROCI (380 Italy), Brigitta SANDER (752 Sweden), Marco PAULLI (380 Italy), Richard ROSENQUIST (752 Sweden) and Meena KANDURI (752 Sweden)

Edition

Epigenetics, Philadelphia, TAYLOR & FRANCIS INC, 2016, 1559-2294

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.394

RIV identification code

RIV/00216224:14740/16:00090836

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1080/15592294.2016.1164375

UT WoS

000377274700002

Keywords in English

Chronic lymphocytic leukemia; DNA methylation; mantle cell lymphoma; microRNA; tumor suppressor

Abstract

V originále

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.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

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. 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.

@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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