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Blood, 1 August 2008, Vol. 112, No. 3, pp. 822-829.
Prepublished online as a Blood First Edition Paper on May 15, 2008; DOI 10.1182/blood-2008-03-142182.
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Submitted March 3, 2008
Accepted April 25, 2008
Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma
Robert W Chen*, Lynne T Bemis, Carol M Amato, Han Myint, Hung Tran, Diane K Birks, S Gail Eckhardt, and William A Robinson
Division of Medical Oncology, University of Colorado Denver School of Medicine, Aurora, CO, United States
* Corresponding author; email: robert.chen{at}uchsc.edu.
Cyclin D1 (CCND1) is a well known regulator of cell cycle progression. It is overexpressed in several types of cancer including breast, lung, squamous, neuroblastoma, and lymphomas. The most well known mechanism of overexpression is the t(11;14)(q13;q32) translocation found in mantle cell lymphoma (MCL). Weistner et al1 have shown that truncated CCND1 mRNA in MCL correlates with poor prognosis. We hypothesized that truncations of the CCND1 mRNA alters its ability to be down regulated by microRNAs in MCL. MicroRNAs are a new class of abundant small RNAs that play important regulatory roles at the post transcriptional level by binding to the 3' untranslated region (UTR) of mRNAs blocking either their translation or initiating their degradation. In this study, we have identified the truncation in CCND1 mRNA in MCL cell lines. We also found that truncated CCND1 mRNA leads to increased CCND1 protein expression and increased S-phase cell fraction. Furthermore, we demonstrated that this truncation alters miR-16-1 binding sites, and through the use of reporter constructs, we were able to show that miR-16-1 regulates CCND1 mRNA expression. This study introduces the role of miR-16-1 in the regulation of CCND1 in MCL.

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