Význam deregulace mikroRNA v molekulární patogenezi a histologické transformaci folikulárního lymfomu
| Title in English | The Importance of MicroRNA Deregulation in the Molecular Pathogenesis and Histological Transformation of Follicular Lymphoma |
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| Authors | |
| Year of publication | 2017 |
| Type | Article in Periodical |
| Magazine / Source | Klinická onkologie |
| MU Faculty or unit | |
| 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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