MicroRNA Profiling in Ocular Adnexal Lymphoma: A Role for MYC and NFKB1 Mediated Dysregulation of MicroRNA Expression in Aggressive Disease
MicroRNA Profiling in Ocular Adnexal Lymphoma: A Role for MYC and NFKB1 Mediated Dysregulation of MicroRNA Expression in Aggressive Disease
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DOI：
10.1167/iovs.13-12272
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发表时间：
2013-08-01
影响因子：
4.4
通讯作者：
Gronbaek, Kirsten
中科院分区：
文献类型：
--
作者：
Hother, Christoffer;Rasmussen, Peter Kristian;Gronbaek, Kirsten
目的。眼附属器淋巴瘤（即累及眼眶、眼睑、结膜、泪腺和泪囊的淋巴瘤）虽然罕见，但在累及眼附属器区域的恶性肿瘤中很常见。主要亚型是低度结外边缘区淋巴瘤 (EMZL) 和侵袭性弥漫性大 B 细胞淋巴瘤 (DLBCL)。据报道，在极少数情况下，低级别 EMZL 会转化为 DLBCL。然而，目前尚不清楚哪些遗传事件能够区分低度疾病和侵袭性、可能致命的疾病。方法。使用 Exiqon 基于 LNA 的阵列，我们对涉及眼附件位点的 18 个 EMZL 和 25 个 DLBCL 进行了全局 microRNA (miRNA) 表达谱分析，以研究低级别疾病与高级别疾病中 miRNA 表达的变化。结果通过实时定量 PCR (RTq-PCR) 得到证实。 结果。我们的分析显示，与 EMZL 相比，DLBCL 中有 43 个 miRNA 的表达谱发生改变。相对于 EMZL，DLBCL 中下调的 7 个 miRNA 显示出癌蛋白 MYC 直接转录抑制的富集。我们还报告了 NFKB1 及其下游 miRNA 可能失去调节。此外，我们的分析还发现了一组 DLBCL，其表达谱与 EMZL 相似。尽管眼附属器区域 EMZL 转化为 DLBCL 的情况很少见，但我们假设中间组可能源自组织学未识别的 EMZL 转化。结论。我们得出的结论是，眼附属器 EMZL 和 DLBCL 之间 miRNA 表达存在根本差异，这主要是由于 MYC 和 NF-kappa B 调控途径的差异。
PURPOSE. Ocular adnexal lymphoma (i.e., lymphoma with involvement of the orbit, eyelids, conjunctiva, lacrimal gland, and lacrimal sac), although rare, is common among malignant tumors involving the ocular adnexal region. The main subtypes are low-grade extranodal marginal zone lymphoma (EMZL) and aggressive diffuse large B-cell lymphoma (DLBCL). In rare cases, low-grade EMZL are reported to transform to DLBCL. It is unclear, however, which genetic events distinguish low-grade disease from aggressive, potentially fatal disease.METHODS. Using LNA-based arrays from Exiqon, we performed global microRNA (miRNA) expression profiling of 18 EMZLs and 25 DLBCLs involving ocular adnexal sites to investigate changes in the miRNA expression in low-versus high-grade disease. Findings were confirmed by real-time quantitative PCR (RTq-PCR).RESULTS. Our analysis revealed 43 miRNAs with altered expression profiles in DLBCL compared to EMZL. Seven of the miRNAs down-regulated in DLBCL relative to EMZL showed enrichment for a direct transcriptional repression by the oncoprotein MYC. We also report a possible loss-of-regulation of NFKB1 and its downstream miRNAs. In addition, our analysis identified a group of DLBCLs whose expression profiles resembled that of EMZL. Although transformation of EMZL to DLBCL in the ocular adnexal region is rare, we hypothesize that the intermediate group potentially may derive from transformation of EMZL that was not recognized by histology.CONCLUSIONS. We conclude that fundamental differences in miRNA expression exist between ocular adnexal EMZL and DLBCL, mainly due to differences in MYC and NF-kappa B regulatory pathways.