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microRNA-34b/c on c...
microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia
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- Deneberg, Stefan (author)
- Karolinska Institutet
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- Kanduri, Meena, 1974 (author)
- 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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Ali, Dina (author)
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Bengtzen, Sofia (author)
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- Karimi, Mohsen (author)
- Karolinska Institutet
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- Qu, Ying (author)
- Karolinska Institutet
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- Kimby, Eva (author)
- Karolinska Institutet
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- Mansouri, Larry (author)
- Uppsala universitet,Hematologi och immunologi
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- Rosenquist, Richard (author)
- Uppsala universitet,Hematologi och immunologi
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- Lennartsson, Andreas (author)
- Karolinska Institutet
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- Lehmann, Sören (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2014-03-31
- 2014
- English.
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In: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 9:6, s. 910-917
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Abstract
Subject headings
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- A commonly deleted region in chronic lymphocytic leukemia (CLL) is the 11q22-23 region, which encompasses the ATM gene. Evidence suggests that tumor suppressor genes other than ATM are likely to be involved in CLL with del(11q). A microRNA (miR) cluster including the miR-34b and miR-34c genes is located, among other genes, within the commonly deleted region (CDR) at 11q. Interestingly, these miRs are part of the TP53 network and have been shown to be epigenetically regulated. In this study, we investigated the expression and methylation status of these miRs in a well-characterized cohort of CLL, including cases with/without 11q-deletion. We show that the miR-34b/c promoter was aberrantly hypermethylated in a large proportion of CLL cases (48%, 25/52 cases). miR-34b/c expression correlated inversely to DNA methylation (P = 0.003), and presence of high H3K37me3 further suppressed expression regardless of methylation status. Furthermore, increased miR-34b/c methylation inversely correlated with the presence of 11q-deletion, indicating that methylation and del(11q) independently silence these miRs. Finally, 5-azacytidine and trichostatin A exposure synergistically increased the expression of miR-34b/c in CLL cells, and transfection of miR-34b or miR-34c into HG3 CLL cells significantly increased apoptosis. Altogether, our novel data suggest that miR-34b/c is a candidate tumor suppressor that is epigenetically silenced in CLL.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (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)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- DNA methylation
- chronic lymphatic leukemia
- epigenetics
- micro-RNA
- chronic lymphatic leukemia
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Deneberg, Stefan
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Kanduri, Meena, ...
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Ali, Dina
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Bengtzen, Sofia
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Karimi, Mohsen
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Qu, Ying
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show more...
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Kimby, Eva
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Mansouri, Larry
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Rosenquist, Rich ...
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Lennartsson, And ...
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Lehmann, Sören
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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NATURAL SCIENCES
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and Biochemistry and ...
- Articles in the publication
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Epigenetics
- By the university
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University of Gothenburg
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Uppsala University
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Karolinska Institutet