Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection
Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection
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DOI：
10.1038/leu.2012.29
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发表时间：
2012-07-01
期刊：
影响因子：
11.4
通讯作者：
Hansmann, M-L
中科院分区：
文献类型：
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作者：
Peveling-Oberhag, J.;Crisman, G.;Hansmann, M-L
脾边缘区淋巴瘤（SMZL）的精确分子发病机制仍不清楚。临床和流行病学数据表明，慢性丙型肝炎病毒 (HCV) 感染可能在部分病例中具有病因学作用。我们通过定量逆转录 PCR (Q-RT-PCR) 对 26 个显微解剖脾组织样本（7 个 HCV+ SMZL；8 个 HCV-SMZL 和 11 个非肿瘤性脾对照）进行了 381 个 miRNA 的大规模 microRNA (miRNA) 表达谱分析。使用单次检测 Q-RT-PCR 和 miRNA 原位杂交 (miRNA-ISH) 来确认独立队列中的结果。 miRNA 表达谱的无监督分层聚类表明，与正常脾边缘区相比，SMZL 具有独特的特征。监督分析揭示了差异表达的 miRNA，包括先前公认的具有肿瘤抑制或致癌潜力的 miRNA。在 SMZL 中发现 5 个 miRNA 显着过表达，包括 miR-21、miR-155 和 miR-146a，而 7 个 miRNA 的表达显着降低，包括 miR-139、miR-345、miR-125a 和 miR-126。此外，我们还发现 miR-26b（一种已知具有肿瘤抑制特性的 miRNA）在 HCV 阳性患者的 SMZL 中显着下调（P = 0.0016）。总之，SMZL 中存在特征性的 miRNA 表达失调，可能与其分子肿瘤发生有关。
The precise molecular pathogenesis of splenic marginal zone lymphoma (SMZL) is still unknown. Clinical and epidemiological data suggest that chronic hepatitis C virus (HCV) infection may have an etiological role in a subset of cases.We performed a large-scale microRNA (miRNA) expression profiling analysis of 381 miRNAs by quantitative reverse transcription PCR (Q-RT-PCR) of 26 microdissected splenic tissue samples (7 HCV+ SMZL; 8 HCV- SMZL and 11 non-neoplastic splenic controls). Single assay Q-RT-PCR and miRNA in situ hybridization (miRNA-ISH) were used to confirm the results in an independent cohort. Unsupervised hierarchical clustering of miRNA expression profiles demonstrated a distinct signature of SMZL compared with the normal splenic marginal zone. Supervised analysis revealed differentially expressed miRNAs, including miRNAs with previously recognized tumor suppressive or oncogenic potential. Five miRNAs were found significantly overexpressed in SMZL, including miR-21, miR-155 and miR-146a, whereas seven miRNAs showed significantly reduced expression, including miR-139, miR-345, miR-125a and miR-126. Furthermore, we identified miR-26b, a miRNA known to have tumor suppressive properties, as significantly downregulated in SMZL arising in HCV-positive patients (P = 0.0016). In conclusion, there is a characteristic dysregulation of miRNA expression in SMZL with a possible implication in its molecular tumorigenesis.