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Epigenetic silencin...
Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression. : Epigenetic inactivation of miR - 26A1 in CLL and MCL
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- Kopparapu, Pradeep Kumar (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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Bhoi, Sujata (författare)
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Mansouri, Larry (författare)
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- Arabanian, Laleh S. (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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Plevova, Karla (författare)
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Pospisilova, Sarka (författare)
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Wasik, Agata M. (författare)
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Croci, Giorgio Alberto (författare)
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Sander, Birgitta (författare)
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Paulli, Marco (författare)
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Rosenquist, Richard (författare)
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- Kanduri, Meena, 1974 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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(creator_code:org_t)
- 2016-05-03
- 2016
- Engelska.
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 11:5, s. 335-343
- Relaterad länk:
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https://www.tandfonl...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- DNA methylation; chronic lymphocytic leukemia; mantle cell lymphoma; microRNA; tumor suppressor
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Kopparapu, Prade ...
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Bhoi, Sujata
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Mansouri, Larry
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Arabanian, Laleh ...
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Plevova, Karla
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Pospisilova, Sar ...
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visa fler...
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Wasik, Agata M.
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Croci, Giorgio A ...
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Sander, Birgitta
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Paulli, Marco
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Rosenquist, Rich ...
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Kanduri, Meena, ...
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Epigenetics
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Göteborgs universitet