Význam deregulace mikroRNA v molekulární patogenezi a histologické transformaci folikulárního lymfomu

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Title in English The Importance of MicroRNA Deregulation in the Molecular Pathogenesis and Histological Transformation of Follicular Lymphoma
Authors

MUSILOVÁ Kateřina DEVÁN Ján ZLÁMALÍKOVÁ Lenka KŘEN Leoš MÓCIKOVÁ H. PROCHÁZKA V. MAYER Jiří TRNĚNÝ Marek JANÍKOVÁ Andrea MRÁZ Marek

Year of publication 2017
Type Article in Periodical
Magazine / Source Klinická onkologie
MU Faculty or unit

Faculty of Medicine

Citation
Field Oncology and hematology
Keywords follicular lymphoma; microRNA; histological transformation
Description Background: Molecular pathogenesis of follicular lymphoma (FL) is characterized by substantial dysregulation of epigenetic regulators. Many cases of FL are associated with the aberrant expression of non-coding regulatory RNAs, namely microRNAs (miRNA). Here we studied changes in miRNA expression and their association with histological transformation of FL to diffuse large B-cell lymphoma (DLBCL). Material and Methods: To identify changes in miRNA levels during FL transformation we performed a global expression analysis of 377 miRNAs in 16 samples (8 pairs) from FL patients vs. transformed FL (tFL) (TLDA miRNA cards; Thermo Fisher Scientific). The association of miRNA expression with clinical-biological characteristics and target proteins were further analyzed in a cohort of 89 FL patients. Results: The miRNA expression profiling of paired FL-tFL samples revealed statistically significant changes in the expression of five miRNAs (p lt; 0.05). Four of them were down-regulated and one was up-regulated in tFL compared to FL. Lower levels of one of these miRNA were also associated with higher proliferation rate of FL cells (Ki-67 gt; 20%), higher FLIPI score ( 3) and shorter overall survival of FL patients. Furthermore, we found that this miRNA regulates the levels of FOXP1 protein in FL. The patients with high-level FOXP1 expression (gt; 70% positive cells) had significantly shorter overall survival in comparison to those with low-level FOXP1 expression (lt; 30% positive cells). Moreover, FOXP1 protein levels were higher in most tFL samples compared to FL before transformation. Conclusion: We found miRNAs associated with the transformation of FL to a more aggressive DLBCL, and described that one of them could serve as a prognostic marker. We found that reduced expression of this tFL-associated miRNA results in increased levels of FOXP1 protein and we assume that the increased activity of FOXP1 proto-oncogene contributes to the histological transformation of FL.
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