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转录因子 Yin Yang 1 及其选择性识别的靶标 Survivin 在高级别 B 细胞非霍奇金淋巴瘤中的作用:潜在的诊断和治疗靶点。

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.

机构信息

Laboratory of Translational Oncology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.

Epidemiology Unit, IRCCS Istituto Nazionale Tumori 'Fondazione G. Pascale', 80131 Naples, Italy.

出版信息

Int J Mol Sci. 2020 Sep 3;21(17):6446. doi: 10.3390/ijms21176446.

DOI:10.3390/ijms21176446
PMID:32899428
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7504013/
Abstract

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 () transcription factor might modulate the expression of apoptotic regulators genes. The present study was aimed to: (1) examine the potential oncogenic role of in reversing drug resistance in B-NHLs; and (2) identify transcriptional target(s) that regulate the apoptotic pathway in B-NHLs. Predictive analyses coupled with database-deposited data suggested that binds the promoter of the /survivin anti-apoptotic gene. Gene Expression Omnibus (GEO) analyses of several B-NHL repositories revealed a conserved positive correlation between and survivin, both highly expressed, especially in aggressive B-NHLs. Further validation experiments performed in Raji Burkitt's lymphomas cells, demonstrated that silencing was associated with survivin downregulation and sensitized the cells to apoptosis. Overall, our results revealed that: (1) and survivin are positively correlated and overexpressed in B-NHLs, especially in BLs; (2) strongly binds to the survivin promoter, hence survivin may be suggested as transcriptional target; (3) silencing sensitizes Raji cells to drug-induced apoptosis via downregulation of survivin; (4) both and survivin are potential diagnostic markers and therapeutic targets for the treatment of resistant/relapsed B-NHLs.

摘要

B 细胞非霍奇金淋巴瘤 (B-NHL) 常表现出对化疗药物的耐药性和/或复发。在药物诱导的细胞凋亡过程中,阴阳 1()转录因子可能调节凋亡调节基因的表达。本研究旨在:(1) 研究 在逆转 B-NHL 耐药中的潜在致癌作用;(2) 确定调节 B-NHL 凋亡途径的 转录靶标。预测分析结合数据库中已保存的数据表明,与抗凋亡基因的启动子结合。几个 B-NHL 存储库的基因表达综合数据库 (GEO) 分析显示,与 survivin 之间存在一致的正相关,两者均高度表达,尤其是在侵袭性 B-NHL 中。在 Raji 伯基特淋巴瘤细胞中进行的进一步验证实验表明,沉默与 survivin 下调相关,并使细胞对凋亡敏感。总体而言,我们的研究结果揭示了:(1) 与 survivin 在 B-NHL 中呈正相关且过表达,尤其是在 BL 中;(2) 与 survivin 启动子强烈结合,因此 survivin 可能是 转录靶标;(3) 沉默通过下调 survivin 使 Raji 细胞对药物诱导的凋亡敏感;(4) 与 survivin 都是耐药/复发 B-NHL 治疗的潜在诊断标志物和治疗靶点。

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