Long noncoding RNA HULC predicts poor clinical outcome and represents pro-oncogenic activity in diffuse large B-cell lymphoma
Long noncoding RNA HULC predicts poor clinical outcome and represents pro-oncogenic activity in diffuse large B-cell lymphoma
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长非编码 RNA HULC 预测较差的临床结果并代表弥漫性大 B 细胞淋巴瘤的促癌活性
DOI：
10.1016/j.biopha.2016.02.032
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发表时间：
2016-04-01
影响因子：
7.5
通讯作者：
Feng, Jifeng
中科院分区：
文献类型：
--
作者：
Peng, Wei;Wu, Jianzhong;Feng, Jifeng
弥漫性大B细胞淋巴瘤(DLBCL)是导致癌症相关死亡的主要原因之一，对现有的治疗方法反应很差。因此，迫切需要寻找新的DLBCL预后标志物和治疗靶点。新出现的研究表明，长非编码RNA(LncRNAs)在多种肿瘤中差异表达，在肿瘤的发生发展中发挥重要作用。此前，本课题组曾报道新的lncRNA HULC在人胰腺癌中具有重要的生物学功能和临床应用潜力。在这里，我们研究了HULC在DLBCL队列中的表达，以评估其表达模式、临床价值和分子机制。首先，我们发现HULC在DLBCL组织和细胞系中均显著过表达。此外，我们还说明HULC与DLBCL的特征密切相关，如Ann Arbor分期、B症状、CHOP样治疗、利妥昔单抗和IPI。重要的是，通过长期的随访，我们从大量样本中证实了HULC是DLBCL诊断和预后的关键预测因素。此外，我们还发现HULC基因敲除可以显著抑制DLBCL细胞的增殖和诱导细胞凋亡，其机制可能是通过抑制细胞周期蛋白D1和Bcl-2的表达。提示HULC可作为反映DLBCL预后不良的新指标，可作为DLBCL诊断和基因治疗的潜在靶点。(C)2016年爱思唯尔·马森SAS。版权所有。
Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of DLBCL. Emerging studies have implicated that long noncoding RNAs (lncRNAs) are differentially expressed in various tumors and play an important role in the development of cancer. Previously, our group has reported that the novel lncRNA HULC has important biological function and clinical potential in human pancreatic cancer. Here, we investigated the expression of HULC in a cohort of DLBCL to assess its expression pattern, clinical value and molecular mechanism. Firstly, we found that HULC was remarkably overexpressed in both DLBCL tissues and cell lines. Moreover, we illustrated that HULC was closely related to DLBCL characteristics, such as Ann Arbor stages, B symptoms, CHOP-like treatment, rituximab and IPI. Importantly, we verified that HULC was an key predictive factor for DLBCL diagnosis and prognosis from sizable samples through the long time follow-ups. Furthermore, we reveal that the HULC knockdown could significantly arrest cell proliferation and induce apoptosis by repressing cyclin D1 and Bcl-2 in DLBCL cells. Our results suggested that HULC could represent a novel indicator of poor prognosis and may be served as a potential target for the diagnosis and gene therapy of DLBCL. (C) 2016 Elsevier Masson SAS. All rights reserved.