miR-31 and miR-17-5p levels change during transformation of follicular lymphoma.
miR-31 and miR-17-5p levels change during transformation of follicular lymphoma.
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DOI：
10.1016/j.humpath.2015.11.011
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发表时间：
2016-04
期刊：
影响因子：
3.3
通讯作者：
Eischen CM
中科院分区：
文献类型：
--
作者：
Thompson MA;Edmonds MD;Liang S;McClintock-Treep S;Wang X;Li S;Eischen CM
惰性滤泡性淋巴瘤转化为侵袭性弥漫性大B细胞淋巴瘤（DLBCL）的患者中有30%的生存率很低。缺乏滤泡性B细胞淋巴瘤转化为DLBCL的可靠预测因子，并且对那些将进展的预测因子的诊断具有挑战性。微小RNA（microRNA，miRNA）是调节基因表达的重要分子，在多种肿瘤的发生、发展过程中发挥重要作用，并参与淋巴瘤的发病机制。使用来自患有滤泡性淋巴瘤并进展为DLBCL的患者的五个配对样本，我们鉴定了两者之间差异表达的特异性miRNA。具体而言，miR-17 - 5p水平在滤泡性淋巴瘤中较低，并随着疾病转化而增加。相比之下，miR-31在滤泡性淋巴瘤中表达较高，并随着淋巴瘤的进展而降低。这些结果在低级别滤泡性淋巴瘤（n = 13）和3级高级别滤泡性淋巴瘤或DLBCL（n = 17）的其他未配对病例中得到证实。DLBCL中miR-31表达的缺失不是由于该位点的缺失。miR-17 - 5p和miR-31的变化与MYC癌基因的免疫表型、遗传学或状态无关。然而，增加的miR-17 - 5p表达确实与增加的TP53蛋白表达显著相关，这指示突变的TP53。两个促增殖基因E2F2和PI3KC2A被鉴定为miR-31的直接mRNA靶点，表明这些基因可能有助于滤泡性淋巴瘤转化。我们的研究结果表明，miR-31和miR-17 - 5 p的变化反映了滤泡性淋巴瘤向侵袭性大B细胞淋巴瘤的转化，并且可能与它们的靶点一起沿着成为该过程的可行标记。
The 30% of patients whose indolent follicular lymphoma transforms to aggressive diffuse large B-cell lymphoma (DLBCL) have poor survival. Reliable predictors of follicular B-cell lymphoma transformation to DLBCL are lacking, and diagnosis of those that will progress is challenging. microRNA (miRNA), which regulate gene expression, have critical functions in the growth and progression of many cancers and contribute to the pathogenesis of lymphoma. Using five paired samples from patients that presented with follicular lymphoma and progressed to DLBCL, we identified specific miRNA differentially expressed between the two. Specifically, miR-17-5p levels were low in follicular lymphoma and increased as the disease transformed. In contrast, miR-31 expression was high in follicular lymphoma and decreased as the lymphoma progressed. These results were confirmed in additional unpaired cases of low-grade follicular lymphoma (n=13) and high-grade follicular lymphoma grade 3 or DLBCL (n=17). Loss of miR-31 expression in DLBCL was not due to deletion of the locus. Changes in miR-17-5p and miR-31 were not correlated with immunophenotype, genetics, or status of the MYC oncogene. However, increased miR-17-5p expression did significantly correlate with increased expression of TP53 protein, which is indicative of mutant TP53. Two pro-proliferative genes, E2F2 and PI3KC2A, were identified as direct mRNA targets of miR-31, suggesting that these may contribute to follicular lymphoma transformation. Our results indicate that changes in miR-31 and miR-17-5p reflect the transformation of follicular lymphoma to an aggressive large B-cell lymphoma and may, along with their targets, be viable markers for this process.