Integrated Analysis of Long Non-Coding RNA and mRNA Expression Profile in Pancreatic Cancer Derived Exosomes Treated Dendritic Cells by Microarray Analysis.

Integrated Analysis of Long Non-Coding RNA and mRNA Expression Profile in Pancreatic Cancer Derived Exosomes Treated Dendritic Cells by Microarray Analysis.
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通过微阵列分析对胰腺癌源性外泌体处理的树突状细胞中长非编码 RNA 和 mRNA 表达谱进行综合分析

DOI:
10.7150/jca.21749
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发表时间:
2018
期刊:
影响因子:
3.9
通讯作者:
Cao L
Cao L
中科院分区:
医学3区
文献类型:
--
作者:
Chen J;Wang S;Jia S;Ding G;Jiang G;Cao L

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背景:胰腺癌是一种毁灭性的疾病,五年生存率低。树突状细胞(Dendritic cells,DCs)是人体内最强的抗原提呈细胞,在免疫应答中起着关键作用。然而,很少有研究调查胰腺癌来源的外泌体(PEXs)在DC介导的免疫逃逸中的作用。长链非编码RNA(lncRNA)和PEX处理的树突状细胞的mRNA的表达谱是未知的。研究方法:我们使用整合lncRNA和mRNA微阵列,以确定来自五个健康供体的PEX处理的DC和正常DC的表达谱。基因本体论(GO),KEGG和癌症基因组学分析进行了鉴定显着的功能,途径,差异表达的mRNA的协会。构建共表达网络以鉴定差异表达的lncRNA和mRNA之间的相关性,并在20名健康供体中使用实时定量PCR进一步验证。AnnoLnc程序用于对lncRNA进行注释分析。结果:我们分别鉴定了3,227和924个在PEX处理的DC中差异表达的lncRNA和mRNA。GO和途径分析揭示了差异表达的mRNA参与许多重要的生物学过程和分子功能。癌症基因组学分析显示,36种差异表达最多的mRNA参与胰腺癌网络,并与许多关键突变基因如TP 53、KRAS、SMAD 4和CDKN 2A相关。LncRNA如ENST 00000560647和mRNA如legumain(lgmn)在PEX处理的DC中差异表达,并且使用RT-qPCR验证数据。结论:据我们所知,这是第一次研究检测与PEX处理的DC相关的lncRNA和mRNA的差异表达。LncRNA如ENST 00000560647和mRNA如Igmn可能在用PEX处理的DC的免疫逃逸中起关键作用。需要进一步的研究来验证这些RNA的功能和关联。
Background: Pancreatic cancer is a devastating disease with a low five-year survival rate. Dendritic cells (DCs), which are the most potent antigen-presenting cells in the human body, play a pivotal role in the immune response. However, few studies have investigated the role of pancreatic cancer-derived exosomes (PEXs) in DC-meditated immune escape. The expression profiles of long noncoding RNAs (lncRNAs) and mRNAs of PEX-treated dendritic cells are unknown. Methods: We used integrated lncRNA and mRNA microarrays to determine the expression profiles of PEX-treated DCs and normal DCs derived from five healthy donors. Gene Ontology (GO), KEGG, and cancer genomics analyses were performed to identify significant functions, pathways, and the associations of differentially expressed mRNAs. A coexpression network was constructed to identify the correlation between differentially expressed lncRNAs and mRNAs and further validated using real-time quantitative PCR in twenty healthy donors. The AnnoLnc program was used to perform an annotation analysis of lncRNAs. Results: We identified 3,227 and 924 differentially expressed lncRNAs and mRNAs, respectively, in PEX-treated DCs. GO and pathway analysis revealed differentially expressed mRNAs involved in many critical biological processes and molecular functions. Cancer genomics analysis revealed that 36 of the most differentially expressed mRNAs were involved in a pancreatic cancer network and were associated with many critical mutated genes such as TP53, KRAS, SMAD4, and CDKN2A. LncRNAs such as ENST00000560647 and mRNAs such as legumain (lgmn) were differentially expressed in PEX-treated DCs, and the data were validated using RT-qPCR. Conclusions: To our knowledge, this is the first study to detect the differential expression of lncRNAs and mRNAs associated with PEX-treated DCs. LncRNAs such as ENST00000560647 and mRNAs such as lgmn might play a critical role in immune escape of DCs treated with PEX. Further investigation is required to validate the functions and associations of these RNAs.
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MicroRNA-323-3p 通过直接抑制 SMAD2 和 SMAD3 抑制胰腺导管腺癌的细胞侵袭和转移。
DOI: 10.18632/oncotarget.7482
发表时间: 2016-03-22
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DOI: 10.1002/cbin.10301
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