Song Guoqi, Song Guorong, Ni Huiyun, Gu Ling, Liu Hong, Chen Baoan, He Bangshun, Pan Yuqin, Wang Shukui, Cho William C
Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China.
Curr Cancer Drug Targets. 2014;14(7):659-70. doi: 10.2174/1568009614666140818211103.
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.
微小RNA（miRNA）是一类非编码RNA分子；它们的失调可能促成癌症发病机制。然而，miRNA功能障碍如何导致弥漫性大B细胞淋巴瘤（DLBCL）的淋巴瘤发生，其机制尚未完全明确。在本研究中，我们分析了miR - 224在四种DLBCL细胞系和168例患者标本中的表达情况。我们发现，与正常B细胞相比，DLBCL中miR - 224的表达下调，但在生发中心B细胞样型和活化B细胞样型之间无统计学差异。通过生物信息学预测和荧光素酶报告基因检测，我们证明miR - 224通过与其3'-非翻译区结合直接下调CD59的表达。我们还对人DLBCL标本进行了CD59的免疫组化染色，并分析了miR - 224、CD59的表达与接受利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松（R-CHOP）统一治疗的DLBCL患者的总生存期/无进展生存期之间的关系。我们发现miR - 224可能促成DLBCL发病机制。最重要的是，miR - 224和CD59的表达可以预测接受R-CHOP治疗的DLBCL患者的反应和预后。
