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