Analysis of Microarray Data on Gene Expression and Methylation to Identify Long Non-coding RNAs in Non-small Cell Lung Cancer.
Analysis of Microarray Data on Gene Expression and Methylation to Identify Long Non-coding RNAs in Non-small Cell Lung Cancer.
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分析基因表达和甲基化的微阵列数据，以鉴定非小细胞肺癌中的长非编码 RNA。
DOI：
10.1038/srep37233
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发表时间：
2016-11-16
影响因子：
4.6
通讯作者：
Qian B
中科院分区：
文献类型：
--
作者：
Feng N;Ching T;Wang Y;Liu B;Lin H;Shi O;Zhang X;Zheng M;Zheng X;Gao M;Zheng ZJ;Yu H;Garmire L;Qian B
为了确定哪些长非编码RNA(LncRNAs)参与了非小细胞肺癌(NSCLC)，我们分析了基因表达和甲基化的微阵列数据。用基因表达芯片和人甲基化450BeadChip检测肿瘤标本的全基因组表达和甲基化情况。通过比较肿瘤与癌旁组织的差异表达和甲基化情况进行分析。利用RT-qPCR和焦磷酸测序在更多的肿瘤样本中验证了与编码基因和DNA甲基化差异表达和相关的LncRNAs。体外实验评价lncRNA对肿瘤细胞的作用。我们鉴定了8,500个在肿瘤组织和非肿瘤组织中差异表达的lncRNA，其中1,504个与mRNA表达相关。其中两个LncRNAs LOC146880和ENST00000439577分别与两个肿瘤相关基因KPNA2和Rcc2的表达呈正相关。LOC146880和ENST00000439577的高表达也与生存不良有关。对LncRNA表达与DNA甲基化关系的分析表明，LOC146880的表达受其启动子DNA甲基化的下调。下调LOC146880或ENST00000439577在肿瘤细胞中的表达可抑制肿瘤细胞的增殖、侵袭和迁移。通过分析基因表达和甲基化的微阵列数据，我们可以识别出两个可能促进非小细胞肺癌进展的LncRNAs，LOC146880和ENST00000439577。
To identify what long non-coding RNAs (lncRNAs) are involved in non-small cell lung cancer (NSCLC), we analyzed microarray data on gene expression and methylation. Gene expression chip and HumanMethylation450BeadChip were used to interrogate genome-wide expression and methylation in tumor samples. Differential expression and methylation were analyzed through comparing tumors with adjacent non-tumor tissues. LncRNAs expressed differentially and correlated with coding genes and DNA methylation were validated in additional tumor samples using RT-qPCR and pyrosequencing. In vitro experiments were performed to evaluate lncRNA’s effects on tumor cells. We identified 8,500 lncRNAs expressed differentially between tumor and non-tumor tissues, of which 1,504 were correlated with mRNA expression. Two of the lncRNAs, LOC146880 and ENST00000439577, were positively correlated with expression of two cancer-related genes, KPNA2 and RCC2, respectively. High expression of LOC146880 and ENST00000439577 were also associated with poor survival. Analysis of lncRNA expression in relation to DNA methylation showed that LOC146880 expression was down-regulated by DNA methylation in its promoter. Lowering the expression of LOC146880 or ENST00000439577 in tumor cells could inhibit cell proliferation, invasion and migration. Analysis of microarray data on gene expression and methylation allows us to identify two lncRNAs, LOC146880 and ENST00000439577, which may promote the progression of NSCLC.
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