Deregulated Expression of miR-224 and its Target Gene: CD59 Predicts Outcome of Diffuse Large B-cell Lymphoma Patients Treated with R-CHOP
Deregulated Expression of miR-224 and its Target Gene: CD59 Predicts Outcome of Diffuse Large B-cell Lymphoma Patients Treated with R-CHOP
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DOI：
10.2174/1568009614666140818211103
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发表时间：
2014-01-01
影响因子：
3
通讯作者：
Cho, William C.
中科院分区：
文献类型：
--
作者：
Song, Guoqi;Song, Guorong;Cho, William C.
miRNA是非编码RNA分子;它们的失调可能有助于癌症发病机制。然而，miRNA功能障碍如何促进弥漫性大B细胞淋巴瘤（DLBCL）的淋巴瘤发生的机制尚未完全确定。在这项研究中，我们分析了miR-224在4种DLBCL细胞系和168例患者标本中的表达。我们发现miR-224在DLBCL中的表达较正常B细胞下调，但在生发中心样B细胞型和活化样B细胞型之间差异无统计学意义。使用生物信息学预测和荧光素酶报告分析，我们证明了miR-224通过结合其3 '非翻译区直接下调CD 59表达。我们还使用了人DLBCL标本中CD 59的免疫组化染色，并分析了miR-224、CD 59表达与DLBCL患者的总体/无进展生存期之间的关系，这些患者均接受利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松（R-CHOP）治疗。我们发现miR-224可能参与DLBCL的发病机制。最重要的是，miR-224和CD 59的表达可以预测用R-CHOP治疗的DLBCL患者的反应和结果。
miRNAs are non-coding RNA molecules; their deregulations may contribute to cancer pathogenesis. However, the mechanisms of how miRNA dysfunction contributes to the lymphomagenesis of diffuse large B-cell lymphoma (DLBCL) are not well established. In this study, we analyzed the expression of miR-224 in four DLBCL cell lines and 168 patients' specimens. We found that the expression of miR-224 in DLBCL was down-regulated compared with normal B-cell but was not statistically different between the germinal center B-cell-like-type and the activated B-cell-like-type. Using bioinformatics prediction and luciferase report assays, we demonstrated that miR-224 directly down-regulated CD59 expression by binding to its 3'-untranslated region. We also used immunohistochemical staining of CD59 in human DLBCL specimens and analyzed the relationship between the expression of miR-224, CD59 and the overall/progress-free survival of DLBCL patients who were uniformly treated with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). We found that miR-224 may contribute to DLBCL pathogenesis. Most importantly, the expression of miR-224 and CD59 can predict the response and outcome of DLBCL patients treated with R-CHOP.