Abstract |
Mantle cell lymphoma (MCL) is one of the most aggressive B-cell lymphomas. Although several protein-coding genes are altered, expression signature and importance of microRNA ( miRNA) have not been well documented in this malignancy. Here, we performed miRNA expression profile in 30 patients with MCL using a platform containing 515 human miRNAs. Eighteen miRNAs were down-regulated and 21 were up-regulated in MCL compared with normal B lymphocytes. The most frequently altered miRNAs are decrease of miR-29a/b/c, miR-142-3p/5p, and miR-150 and increase of miR-124a and miR-155. Notably, expression levels of miR-29 family are associated with prognosis. The patients with significant down-regulated miR-29 had short survival compared with those who express relatively high levels of miR-29. The prognostic value of miR-29 is comparable with the Mantle Cell Lymphoma International Prognostic Index. Furthermore, we demonstrate miR-29 inhibition of CDK6 protein and mRNA levels by direct binding to 3'-untranslated region. Inverse correlation between miR-29 and CDK6 was observed in MCL. Because cyclin D1 overexpression is a primary event and exerts its function through activation of CDK4/CDK6, our results in primary MCL cells indicate that down-regulation of miR-29 could cooperate with cyclin D1 in MCL pathogenesis. Thus, our findings provide not only miRNA expression signature but also a novel prognostic marker and pathogenetic factor for this malignancy.
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Authors | Jian-Jun Zhao, Jianhong Lin, Tint Lwin, Hua Yang, Jianping Guo, William Kong, Sophie Dessureault, Lynn C Moscinski, Dorna Rezania, William S Dalton, Eduardo Sotomayor, Jianguo Tao, Jin Q Cheng |
Journal | Blood
(Blood)
Vol. 115
Issue 13
Pg. 2630-9
(Apr 01 2010)
ISSN: 1528-0020 [Electronic] United States |
PMID | 20086245
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- 3' Untranslated Regions
- Biomarkers, Tumor
- CCND1 protein, human
- MIRN29a microRNA, human
- MicroRNAs
- Neoplasm Proteins
- RNA, Neoplasm
- Cyclin D1
- CDK6 protein, human
- Cyclin-Dependent Kinase 6
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Topics |
- 3' Untranslated Regions
(genetics)
- Aged
- Aged, 80 and over
- B-Lymphocytes
(metabolism)
- Biomarkers, Tumor
- Cyclin D1
(physiology)
- Cyclin-Dependent Kinase 6
(antagonists & inhibitors, biosynthesis, genetics)
- Down-Regulation
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
(genetics)
- Gene Knockdown Techniques
- Humans
- Lymphoma, Mantle-Cell
(etiology, genetics, metabolism)
- Male
- MicroRNAs
(biosynthesis, genetics, physiology)
- Middle Aged
- Neoplasm Proteins
(antagonists & inhibitors, biosynthesis, genetics)
- Prognosis
- RNA, Neoplasm
(biosynthesis, genetics, physiology)
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