Analysis of long non-coding RNA expression profile in papillary thyroid carcinoma
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摘要: 目的 长链非编码RNA (lncRNA)在肿瘤的发生和发展中起重要作用。本研究使用基因芯片技术筛选甲状腺乳头状癌中差异表达的lncRNA,并对这些lncRNA调控的靶基因进行预测和分析。 方法 本研究使用微阵列来研究3例甲状腺乳头状癌(PTC)和配对的邻近非癌性甲状腺组织中lncRNA的表达。基因功能通过GO (Gene Ontology,GO)和通路分析进行评估,并预测lncRNA潜在的靶基因。 结果 与邻近的非癌性甲状腺组织相比,共有855个差异表达lncRNA,上调195个,下调660个(FC>2,P<0.05);2 370个差异表达mRNA,上调801个,下调1 569个(FC>2,P<0.05)。其中差异较大的lncRNA有23个,mRNA有79个(FC>4)。lncRNA-SLC34A2和它相关的mRNA GRCh38(NM_001177998)差异表达最为显著(FC=23.5)。差异表达的mRNA中显著富集的GO途径显示:一些与肿瘤有关,如“焦粘连”“ECM-受体相互作用”“MAPK信号传导途径”和“PI3K/AKT信号传导途径”。经过通路分析,42条信号通路在差异表达的转录后显著富集,其中“焦粘连”最为显著(P=8.499×10-7)并与47个差异表达基因有关。239个与其相关mRNA的lncRNAs可能与顺式调控有关。lncRNAs和mRNAs的位点之间的相对位置关系在基因的不同位点。 结论 本研究是甲状腺肿瘤相关的LNCRNA谱的补充,发现了一定数量的差异表达的LNCRNA,并预测其功能靶向基因和途径。今后,笔者将选择更多的样本,深化对lncRNA分子机制和生化功能的研究,为甲状腺癌的早期诊断和治疗提供新的准确方法。Abstract: Objective Long noncoding RNAs (lncRNAs) play an important role in cancer growth and development. Gene chip technology was used in this study to screen the differential expression lncRNA in papillary thyroid cancer. Targeted genes regulated by these lncRNA were predicted and analyzed. Methods Microarray was used in this study to investigate the lncRNA expression in three paired samples of papillary thyroid cancer (PTC) and paired adjacent noncancerous thyroid tissue. Gene function was evaluated by Gene Ontology (GO) and pathway analysis. Potential target genes of lncRNAs were also predicted. Results Compared with the adjacent noncancerous thyroid tissue, a total of 855 lncRNAs displayed differential expression in tumor tissues, including 195 up-regulated lncRNAs and 660 down-regulated lncRNAs (FC>2, P<0.05). 2 370 differently expressed mRNAs were found of which 801 were upregulated and 1 569 were downregulated (FC>2, P<0.05). Among them, the more differential expression lncRNAs were 23, while mRNA were 79 (FC>4). lncRNA-SLC34A2 with its related mRNA GRCh38 (NM_001177998) was the most dysregulated lncRNA and mRNA with a FC of 23.5. Significantly enriched GO terms and pathways among differentially expressed mRNAs were identified. Some were related to cancer, such as "Focal adhesion", "ECM-receptor interaction", "MAPK signaling pathway" and "PI3K/AKT signaling pathway". Forty-two pathways were significantly enriched among the differentially expressed transcripts showed by pathways analysis (P<0.05). Among them, 'Focal adhesion' (P=8.499×10-7) was the most enriched pathway which was directly associated with 47 differential expressed genes. In all, 239 lncRNAs with its related mRNAs may be associated with cis-regulation. The relative positional relationship between the locus of lnRNAs and mRNAs were in different site of the gene. Conclusions Our study is the supplement to the related lncRNA profile of thyroid tumor. We found certain numbers of differentially expressed lncRNAs and predict its functional targeted genes and pathways. In the future, we will select greater numbers of samples to deepen the research into the lncRNA molecular mechanism and biochemical function, in order to provide a novel accurate method for the early diagnosis and therapy of thyroid cancer.
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Key words:
- Papillary thyroid carcinoma /
- lncRNA /
- Microarray
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