Abstract 2097: microRNA profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma

Abstract

Abstract ABSTRACT: Mantle cell lymphoma (MCL) is one of the most aggressive B-cell lymphomas. While a number of 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 downregulated and 21 were upregulated in MCL when 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 as compared to those who express relative high level of miR-29. Prognostic value of miR-29 is comparable with MIPI (MCL International Prognostic Index). Furthermore, we demonstrate miR-29 inhibition of CDK6 protein and mRNA levels by direct binding to 3′UTR. Inverse correlation between miR-29 and CDK6 was observed in MCL. Since cyclin D1 overexpression is a primary event and exerts its function through activation of CDK4/6, our results in primary MCL cells indicates that downregulation 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. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2097.