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长链非编码RNA HULC预测弥漫性大B细胞淋巴瘤的临床预后不良并表现出促癌活性。

Long noncoding RNA HULC predicts poor clinical outcome and represents pro-oncogenic activity in diffuse large B-cell lymphoma.

作者信息

Peng Wei, Wu Jianzhong, Feng Jifeng

机构信息

Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing Medical University, No. 42 Baiziting Road, Nanjing 210009, China.

Center of Clinical Cancer Research, Jiangsu Cancer Hospital, Nanjing Medical University, No. 42 Baiziting Road, Nanjing 210009, China.

出版信息

Biomed Pharmacother. 2016 Apr;79:188-93. doi: 10.1016/j.biopha.2016.02.032. Epub 2016 Mar 7.

DOI:10.1016/j.biopha.2016.02.032
PMID:27044827
Abstract

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.

摘要

弥漫性大B细胞淋巴瘤(DLBCL)是癌症相关死亡的主要原因之一,对现有治疗反应不佳。因此,迫切需要确定DLBCL的新型预后标志物和治疗靶点。新兴研究表明,长链非编码RNA(lncRNA)在各种肿瘤中差异表达,并在癌症发展中发挥重要作用。此前,我们小组报道了新型lncRNA HULC在人类胰腺癌中具有重要的生物学功能和临床潜力。在此,我们研究了HULC在一组DLBCL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,我们还表明HULC与DLBCL的特征密切相关,如Ann Arbor分期、B症状、CHOP样治疗、利妥昔单抗和国际预后指数(IPI)。重要的是,通过长时间随访,我们从大量样本中验证了HULC是DLBCL诊断和预后的关键预测因素。此外,我们发现敲低HULC可通过抑制DLBCL细胞中的细胞周期蛋白D1和Bcl-2显著抑制细胞增殖并诱导凋亡。我们的结果表明,HULC可能是预后不良的新指标,并可能成为DLBCL诊断和基因治疗的潜在靶点。

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