The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR-223 in extranodal NK/T-cell lymphoma, nasal type.
The downregulation of PRDM1/Blimp-1 is associated with aberrant expression of miR-223 in extranodal NK/T-cell lymphoma, nasal type.
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DOI：
10.1186/1756-9966-33-7
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发表时间：
2014-01-17
期刊：
影响因子：
--
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Liang L;Nong L;Zhang S;Zhao J;Ti H;Dong Y;Zhang B;Li T
新发现的结外NK/T细胞鼻型淋巴瘤(EN-NK/T-NT)抑癌基因PRDM1失活的机制尚不清楚。本研究的目的是研究PRDM1在EN-NK/T-NT中的表达，并分析miRNAs对其的下调作用。采用免疫组织化学、定量逆转录聚合酶链式反应和原位杂交法检测PRDM1和miRNA在EN-NK/T-NT组织中的表达。荧光素酶检测证实miR-223与PRDM1mRNA的3‘-非翻译区直接结合。此外，通过转染miR-223模拟物或抑制物来增加或降低miR-223的有效表达，观察了miR-223对NK/T淋巴瘤细胞株PRDM1表达的影响。采用Kaplan-Meier单因素分析和LOG-RANK检验分析EN-NK/T-NT患者的总生存期和无失败生存期。对EN-NK/T-NT患者PRDM1表达下调的研究表明，PRDM1阳性染色可能是预测EN-NK/T-NT患者总生存期和无失败生存期的良好指标。然而，PRDM1的阴性染色通常是转录本，表明可能是转录后调控。MIR-223及其可能的靶基因PRDM1在EN-NK/T-NT组织和细胞系中的表达模式相反。荧光素酶分析表明，PRDM1基因是miR-223的直接靶基因。异位表达miR-223导致NK/T细胞淋巴瘤细胞株PRDM1蛋白表达下调，而miR-223表达降低则恢复PRDM1蛋白水平。我们的研究结果表明，抑癌基因PRDM1在EN-NK/T-NT中的下调是由miR-223介导的，PRDM1阳性染色可能对评估EN-NK/T-NT患者的临床预后有一定的价值。
The mechanism for inactivation of positive regulatory domain containing I (PRDM1), a newly identified tumour suppressor gene in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT) has not been well defined. The aim of the present study was to investigate the expression of PRDM1 in EN-NK/T-NT and analyse its downregulation by miRNAs. PRDM1 and miRNA expression were evaluated in EN-NK/T-NT samples by immunohistochemical analysis, qRT-PCR, and in situ hybridisation. Luciferase assays were performed to verify the direct binding of miR-223 to the 3′-untranslated region of PRDM1 mRNA. In addition, the effect of miR-223 on PRDM1 expression was assessed in NK/T lymphoma cell lines by transfecting a miR-223 mimic or inhibitor to increase or decrease the effective expression of miR-223. Overall survival and failure-free survival in EN-NK/T-NT patients were analysed using Kaplan-Meier single-factor analysis and the log-rank test. Investigation of the downregulation of PRDM1 in EN-NK/T-NT cases revealed that PRDM1-positive staining might be a favourable predictor of overall survival and failure-free survival in EN-NK/T-NT patients. However, the negative staining of PRDM1 usually presented transcripts, suggesting a possible post-transcriptional regulation. miR-223 and its putative target gene, PRDM1, exhibited opposite patterns of expression in EN-NK/T-NT tissues and cell lines. Moreover, PRDM1 was identified as a direct target gene of miR-223 by luciferase assays. The ectopic expression of miR-223 led to the downregulation of the PRDM1 protein in the NK/T-cell lymphoma cell line, whereas a decrease in miR-223 restored the level of PRDM1 protein. Our findings reveal that the downregulation of the tumour suppressor PRDM1 in EN-NK/T-NT samples is mediated by miR-223 and that PRDM1-positive staining might have prognostic value for evaluating the clinical outcome of EN-NK/T-NT patients.
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影响因子：
6
作者：
Nie, Kui;Zhang, Taotao;Tam, Wayne
通讯作者：
Tam, Wayne
DOI：
10.1186/2043-9113-3-6
发表时间：
2013-03-16
期刊：
Journal of clinical bioinformatics
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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Rajewsky K
影响因子：
50.3
作者：
Mandelbaum J;Bhagat G;Tang H;Mo T;Brahmachary M;Shen Q;Chadburn A;Rajewsky K;Tarakhovsky A;Pasqualucci L;Dalla-Favera R
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Dalla-Favera R
DOI：
10.1073/pnas.1115128108
发表时间：
2011-12-13
影响因子：
11.1
作者：
Kuecuek, Can;Iqbal, Javeed;Chan, Wing C.
通讯作者：
Chan, Wing C.