期刊
BLOOD
卷 115, 期 13, 页码 2630-2639出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-09-243147
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资金
- National Institutes of Health [CA137041, CA107078]
- Department of Defense [W81XWH-08-1-0444, W81XWH-08-2-0101, W81XWH-08-1-0116]
- Bankhead-Coley [09BB-05]
- Leukemia Research Foundation
- Lymphoma Research Foundation
- NATIONAL CANCER INSTITUTE [R01CA077859, R01CA137041, R01CA107078] Funding Source: NIH RePORTER
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 downregulated 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. (Blood. 2010;115(13):2630-2639)
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