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Epigenetic silencin...
Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma : Impact on EZH2 expression
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- Kopparapu, Pradeep Kumar (författare)
- Gothenburg Univ, Sahlgrenska Acad, Inst Biomed, Dept Clin Chem & Transfus Med, S-41124 Gothenburg, Sweden.
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- Bhoi, Sujata (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Mansouri, Larry (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Arabanian, Laleh S. (författare)
- Gothenburg Univ, Sahlgrenska Acad, Inst Biomed, Dept Clin Chem & Transfus Med, S-41124 Gothenburg, Sweden.
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- Plevova, Karla (författare)
- Masaryk Univ, Cent European Inst Technol, CS-60177 Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic.
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- Pospisilova, Sarka (författare)
- Masaryk Univ, Cent European Inst Technol, CS-60177 Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic.
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- Wasik, Agata M. (författare)
- Karolinska Institutet
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- Croci, Giorgio Alberto (författare)
- Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy.
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- Sander, Birgitta (författare)
- Karolinska Institutet
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- Paulli, Marco (författare)
- Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy.
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- Rosenquist, Richard (författare)
- Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.
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- Kanduri, Meena (författare)
- Gothenburg Univ, Sahlgrenska Acad, Inst Biomed, Dept Clin Chem & Transfus Med, S-41124 Gothenburg, Sweden.
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Gothenburg Univ, Sahlgrenska Acad, Inst Biomed, Dept Clin Chem & Transfus Med, S-41124 Gothenburg, Sweden Experimentell och klinisk onkologi (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://urn.kb.se/re...
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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 -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Chronic lymphocytic leukemia
- DNA methylation
- mantle cell lymphoma
- microRNA
- tumor suppressor
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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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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Uppsala universitet
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Karolinska Institutet