BCL11A Is Oncogenic and Predicts Poor Outcomes in Natural Killer/T-Cell Lymphoma
BCL11A Is Oncogenic and Predicts Poor Outcomes in Natural Killer/T-Cell Lymphoma
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BCL11A 具有致癌性，可预测自然杀伤/T 细胞淋巴瘤的不良结局
DOI：
10.3389/fphar.2020.00820
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发表时间：
2020-06-04
影响因子：
5.6
通讯作者：
Wang, Hua
中科院分区：
文献类型：
--
作者：
Shi, Hongyun;Li, Chun;Wang, Hua
目前对晚期/复发患者中的自然杀伤/T细胞淋巴瘤（NKTL）的治疗不令人满意，从而突出了对新的治疗靶点的需求。B细胞慢性淋巴细胞性白血病/淋巴瘤11 A（BCL 11 A）作为一种转录因子，在多种肿瘤中具有致癌性。然而，其在NKTL中的功能仍不清楚。实时定量聚合酶链反应和Western印迹分析被用来测量NKTL患者和NKTL细胞系中BCL 11 A的表达水平。来自健康受试者的自然杀伤（NK）细胞用作阴性对照。使用小干扰RNA瞬时转染来敲低NKTL细胞系中的表达。从343名NKTL患者（分为测试组和验证组）收集样本和临床病史，以评估BCL 11 A表达水平的临床价值。在NKTL患者和NKTL细胞系中，BCL 11 A表达上调。在NKTL细胞系中，在BCL 11 A沉默后观察到细胞增殖减少和细胞凋亡增加。NKTL中BCL 11 A表达水平与RUNX 3、c-MYC和P53相关。值得注意的是，BCL 11 A高表达与NKTL的不良临床特征相关，并预测预后不良。总之，BCL 11 A在NKTL中过表达，而其上调促进肿瘤发展。因此，BCL 11 A表达水平可能是NKTL的一个有希望的预后生物标志物。
The current treatment for natural killer/T-cell lymphoma (NKTL) among advanced/relapsed patients is unsatisfying, thereby highlighting the need for novel therapeutic targets. B-cell chronic lymphocytic leukemia/lymphoma 11 A (BCL11A), as a transcription factor, is oncogenic in several neoplasms. However, its function in NKTL remains unclear. Quantitative real-time polymerase chain reaction and Western blot analysis were used to measure the BCL11A expression levels among NKTL patients and in NKTL cell lines. Natural killer (NK) cells from healthy subjects were used as negative control. Transient transfection with small interfering RNA was used to knockdown the expression in NKTL cell lines. Samples and clinical histories were collected from 343 NKTL patients (divided into test and validation groups) to evaluate the clinical value of BCL11A expression level. The BCL11A expression was upregu\lated among NKTL patients and in NKTL cell lines. Reduced cell proliferation and increased apoptosis were observed after silencing BCL11A in NKTL cell lines. BCL11A expression level was correlated with RUNX3, c-MYC, and P53 in NKTL. Notably, a high BCL11A expression was correlated with unfavorable clinical characteristics and predicted poor outcomes in NKTL. In conclusion, BCL11A was overexpressed in NKTL, while its upregulation promoted tumor development. Therefore, BCL11A expression level may be a promising prognostic biomarker for NKTL.