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一种新型长链非编码RNA LINC01133在肺鳞状细胞癌中上调并可预测生存情况。

A novel long noncoding RNA LINC01133 is upregulated in lung squamous cell cancer and predicts survival.

作者信息

Zhang Jing, Zhu Ning, Chen Xiaodong

机构信息

Department of Respiratory Disease, Huashan Hospital, Fudan University, No. 12 Wulumuqi Middle Road, Shanghai, 200040, China.

出版信息

Tumour Biol. 2015 Sep;36(10):7465-71. doi: 10.1007/s13277-015-3460-9. Epub 2015 Apr 24.

Abstract

Lung adenocarcinoma (LAD) and lung squamous cell cancer (LSCC) are two major histological types of non-small cell lung cancer. LSCC differs greatly from LAD in many aspects. Accumulating evidence has shown that long noncoding RNA (lncRNA) plays an important role in the process of carcinogenesis and tumor progression. Expression of lncRNA is highly tissue-specific and could be biomarkers for cancer diagnosis and prognosis. Here, we identified differentially expressed lncRNA between LSCC and LAD by data mining of Affymetrix HG-U133 Plus 2.0 microarray. A set of 1646 differentially expressed lncRNA transcripts were identified. Among these lncRNAs, a novel lncRNA, LINC01133, showed the largest fold change among large intergenic noncoding RNAs. Quantitative real-time polymerase chain reaction (PCR) assay confirmed that LINC01133 was upregulated in LSCC (increasing fold 6.4, P < 0.01) but not in the LAD samples. LSCC patients with higher expression level of LINC01133 had shorter survival time (hazard ratio = 2.383; 95 % confidence interval 1.023-5.547, P = 0.044). Wound-healing and transwell assays demonstrated that silence of LINC01133 by small interfering RNA (siRNA) inhibited invasion ability of LSCC cell line. Thus, a set of lncRNA was differentially expressed between LAD and LSCC and could serve as potential biomarkers.

摘要

肺腺癌(LAD)和肺鳞状细胞癌(LSCC)是非小细胞肺癌的两种主要组织学类型。LSCC在许多方面与LAD有很大差异。越来越多的证据表明,长链非编码RNA(lncRNA)在致癌过程和肿瘤进展中起重要作用。lncRNA的表达具有高度的组织特异性,可作为癌症诊断和预后的生物标志物。在此,我们通过对Affymetrix HG-U133 Plus 2.0芯片数据挖掘,鉴定了LSCC和LAD之间差异表达的lncRNA。共鉴定出1646个差异表达的lncRNA转录本。在这些lncRNA中,一种新型lncRNA,LINC01133,在大型基因间非编码RNA中显示出最大的倍数变化。定量实时聚合酶链反应(PCR)分析证实,LINC01133在LSCC中上调(增加倍数为6.4,P < 0.01),但在LAD样本中未上调。LINC01133表达水平较高的LSCC患者生存时间较短(风险比=2.383;95%置信区间1.023-5.547,P=0.044)。伤口愈合和Transwell实验表明,小干扰RNA(siRNA)沉默LINC01133可抑制LSCC细胞系的侵袭能力。因此,一组lncRNA在LAD和LSCC之间差异表达,可作为潜在的生物标志物。

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