张杰, 刘索, 甘毅, 金龙玉. 非小细胞肺癌中lncRNA DLEU1的表达对肿瘤细胞转移的影响[J]. 中国肿瘤临床, 2018, 45(23): 1181-1186. DOI: 10.3969/j.issn.1000-8179.2018.23.013
引用本文: 张杰, 刘索, 甘毅, 金龙玉. 非小细胞肺癌中lncRNA DLEU1的表达对肿瘤细胞转移的影响[J]. 中国肿瘤临床, 2018, 45(23): 1181-1186. DOI: 10.3969/j.issn.1000-8179.2018.23.013
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Zhang Jie, Liu Suo, Gan Yi, Jin Longyu. Expression of lncRNA DLEU1 in non-small cell lung cancer and its effect on metastasis[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2018, 45(23): 1181-1186. DOI: 10.3969/j.issn.1000-8179.2018.23.013
Citation: Zhang Jie, Liu Suo, Gan Yi, Jin Longyu. Expression of lncRNA DLEU1 in non-small cell lung cancer and its effect on metastasis[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2018, 45(23): 1181-1186. DOI: 10.3969/j.issn.1000-8179.2018.23.013
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非小细胞肺癌中lncRNA DLEU1的表达对肿瘤细胞转移的影响

Expression of lncRNA DLEU1 in non-small cell lung cancer and its effect on metastasis

    摘要
  • 摘要:
      目的  研究长片段非编码RNA（long non-coding RNA，lncRNA）淋巴细胞白血病缺失基因1（deleted in lymphocytic leukemia 1，DLEU1）在非小细胞肺癌（non-small cell lung cancer，NSCLC）中的表达模式和临床意义，并进一步评估其对肿瘤转移的影响。
      方法  42例NSCLC患者配对的癌组织和癌旁组织于2008年1月至2012年12月在中南大学湘雅三医院经手术切除获得。采用实时定量聚合酶链反应检测NSCLC组织和细胞中DLEU1的表达特征。运用统计学方法分析DLEU1的表达与NSCLC患者临床病理特征及生存时间的关系。通过体外伤口愈合和细胞侵袭试验分析DLEU1对NSCLC细胞迁移及侵袭的影响。运用蛋白质印迹法检测DLEU1对NSCLC细胞上皮间质转化（EMT）的标志物（E-钙粘蛋白、N-钙黏蛋白和波形蛋白）表达量的影响。
      结果  42例NSCLC样本中，DLEU1的表达在35例中表现出上调（83.33%），而在7例中表现出下调（16.67%）。DLEU1在NSCLC癌组织的表达量是癌旁组织的2.11倍（P < 0.05）。DLEU1在4种NSCLC细胞系（A549、H1299、SPCA1和H358）的表达量均高于正常肺16HBE上皮细胞，其中，A549细胞中DLEU1表达量最高（P < 0.05）。高表达的DLEU1与淋巴结转移呈正相关（P < 0.05），但与其他参数无显著相关性，包括患者性别、年龄、吸烟史、原发肿瘤大小、组织学分级和TNM分期。与低DLEU1表达组患者相比，高表达组患者生存时间显著缩短（P < 0.05）。与对照组相比，体外干扰DLEU1的表达可显著抑制A549和SPCA1细胞的迁移和侵袭能力（P < 0.05）。与对照组相比，体外干扰DLEU1可显著增加A549细胞中E-钙黏蛋白表达量，而降低N-钙黏蛋白和波形蛋白表达量（P < 0.05）。
      结论  DLEU1在NSCLC组织和细胞系中表达上调，并与患者淋巴结转移和生存时间相关，且具有通过EMT促进肿瘤细胞迁移和侵袭的功能，表明DLEU1可能作为NSCLC的潜在治疗靶点。

     

    Abstract:
      Objective  To investigate the expression pattern and clinical significance of long non-coding RNA deleted in lymphocytic leukemia 1 (DLEU1) in non-small cell lung cancer (NSCLC), and to further evaluate its effect on tumor metastasis.
      Methods  Paired cancer and adjacent tissues were obtained from 42 patients with NSCLC that underwent surgical resection of cancer in The Third Xiangya Hospital of Central South University from January 2008 to December 2012, at the Department of Cardiothoracic Surgery. The expression features of DLEU1 in NSCLC tissue were detected by real-time quantitative polymerase chain reaction assay. Statistical methods were used to analyze the relationship between the expression of DLEU1 and the clinicopathological features and the survival time of patients with NSCLC. Effects of DLEU1 on migration and invasion of NSCLC cells were evaluated by in vitro wound healing and cell invasion assays, respectively. Western blot was performed to investigate the protein levels of Ecadherin, Ncadherin, and Vimentin, which are the biomarkers of epithelial to mesenchymal transition (EMT).
      Results  Of the 42 NSCLC samples, DLEU1 expression was up-regulated in 35 samples (83.33%) and down-regulated in 7 samples (16.67%). The expression level of DLEU1 in NSCLC tissue was 2.11 times that in the adjacent tissues (P < 0.05). The expression of DLEU1 in four NSCLC cell lines (A549, H1299, SPCA1, and H358) was higher than that in normal lung 16HBE epithelial cells, and of these, A549 cells had the highest DLEU1 expression (P < 0.05). Highly expressed DLEU1 was positively correlated with lymph-node metastasis (P < 0.05), but was not significantly associated with other parameters, including patient gender, age, smoking history, primary tumor size, histological grade, and the TNM stage. The survival time of patients with high DLEU1 expression was significantly shorter than that of patients with low DLEU1 expression (P < 0.05). In vitro interference with DLEU1 expression significantly inhibited the migration and invasion of A549 and SPCA1 cells compared with that of the control group (P < 0.05). Upon interference with DLEU1 expression, protein levels of E-cadherin increased, whereas those of N-cadherin and Vimentin decreased in A549 cells in comparison with the control group.
      Conclusions  The expression of DLEU1 is up-regulated in NSCLC tissues and cell lines, correlates with lymph-node metastasis and survival times in patients with NSCLC, and promotes tumor cell migration and invasion by regulating EMT, suggesting that DLEU1 may be a potential therapeutic target for NSCLC.

     

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