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首页> 外文期刊>International Journal of Molecular Sciences >Role of the Transcription Factor Yin Yang 1 and Its Selectively Identified Target Survivin in High-Grade B-Cells Non-Hodgkin Lymphomas: Potential Diagnostic and Therapeutic Targets
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Role of the Transcription Factor Yin Yang 1 and Its Selectively Identified Target Survivin in High-Grade B-Cells Non-Hodgkin Lymphomas: Potential Diagnostic and Therapeutic Targets

机译：转录因子yin yang 1的作用及其在高级B细胞非霍奇金淋巴瘤中的靶发素Survivin：潜在的诊断和治疗目标

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摘要

B-cell non-Hodgkin lymphomas (B-NHLs) are often characterized by the development of resistance to chemotherapeutic drugs and/or relapse. During drug-induced apoptosis, Yin Yang 1 ( YY1 ) transcription factor might modulate the expression of apoptotic regulators genes. The present study was aimed to: (1) examine the potential oncogenic role of YY1 in reversing drug resistance in B-NHLs; and (2) identify YY1 transcriptional target(s) that regulate the apoptotic pathway in B-NHLs. Predictive analyses coupled with database-deposited data suggested that YY1 binds the promoter of the BIRC5 /survivin anti-apoptotic gene. Gene Expression Omnibus (GEO) analyses of several B-NHL repositories revealed a conserved positive correlation between YY1 and survivin, both highly expressed, especially in aggressive B-NHLs. Further validation experiments performed in Raji Burkitt’s lymphomas cells, demonstrated that YY1 silencing was associated with survivin downregulation and sensitized the cells to apoptosis. Overall, our results revealed that: (1) YY1 and survivin are positively correlated and overexpressed in B-NHLs, especially in BLs; (2) YY1 strongly binds to the survivin promoter, hence survivin may be suggested as YY1 transcriptional target; (3) YY1 silencing sensitizes Raji cells to drug-induced apoptosis via downregulation of survivin; (4) both YY1 and survivin are potential diagnostic markers and therapeutic targets for the treatment of resistant/relapsed B-NHLs.
机译：B细胞非霍奇金淋巴瘤（B-NHLs）通常是通过对化学治疗药物和/或复发的抗性的发展的特征。在药物诱导的细胞凋亡期间，阴阳1（YY1）转录因子可能调节凋亡调节剂基因的表达。本研究旨在：（1）检测YY1在B-NHLS中耐药性造成致毒性的潜在致癌作用; （2）识别调节B-NHL中凋亡途径的YY1转录靶标。预测分析与数据库沉积的数据相结合，表明YY1结合了BirC5 / Survivin抗凋亡基因的启动子。几种B-NHL储存库的基因表达综合征（Geo）分析揭示了YY1和Survivin之间的保守正相关，尤其是侵袭性B-NHL。在Raji Burkitt的淋巴瘤细胞中进行的进一步验证实验表明，YY1沉默与Survivin下调相关，并使细胞敏感到细胞凋亡。总体而言，我们的研究结果显示：（1）YY1和Survivin在B-NHL中呈正相关和过表达，特别是在BLS中; （2）YY1强烈与Survivin启动子结合，因此Survivin可以提出作为YY1转录目标; （3）YY1沉默使Raji细胞通过Survivin的下调致药物诱导的细胞凋亡; （4）YY1和Survivin都是治疗抗性/复发的B-NHL的潜在诊断标记和治疗靶标。

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