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全面分析长非编码 RNA 在肺结核发病机制中的表达模式。

Comprehensive analysis of long non-coding RNAs expression pattern in the pathogenesis of pulmonary tuberculosis.

机构信息

School of Biology & Basic Medical Science, Soochow University, Suzhou 215123, China.

Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

出版信息

Genomics. 2020 Mar;112(2):1970-1977. doi: 10.1016/j.ygeno.2019.11.009. Epub 2019 Nov 20.

Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) play crucial roles in the progression and pathogenesis of cancer. Right now, less is known about the association between the expression of lncRNAs and the pathogenesis of pulmonary tuberculosis (PTB).

METHODS

In present study, the expression profiles of lncRNAs were investigated by transcriptome sequencing from PTB patients vs. healthy individuals.

RESULTS

A total of 449 differentially expressed (DE) (fold change ≥2, false discovery rate ≤ 0.05) lncRNAs were screened out from the PTB patients. Lnc-HNRNPU-1:7 and lnc-FAM76B-4:1 was found the most upregulated lncRNAs and downregulated lncRNAs in PTB patients, respectively. GO annotation and KEGG analysis were used to explore the potential roles of these DE lncRNAs. The JAK/STAT and TGF-β signaling pathways related to PTB pathogenesis were enriched in PTB patients. The co-expressed of a few lncRNAs and mRNAs on chromosome were shown by cis-regulatory gene analysis. Trans analysis indicated that STAT1, STAT2 and TAF7 transcription factors regulated the expression of lncRNA and mRNA. The constructed lncRNA ceRNA network suggested that lncRNAs regulating mRNAs expression may mediate by sponged miRNAs.

CONCLUSION

We comprehensively analyzed the expression profiles of lncRNAs in PTB patients, thus providing new clues for exploring the regulatory mechanisms of dysregulated lncRNAs in the pathogenesis of PTB.

摘要

背景

长非编码 RNA(lncRNA)在癌症的发生和发病机制中发挥着关键作用。目前,lncRNA 的表达与肺结核(PTB)发病机制之间的关联还知之甚少。

方法

本研究通过对 PTB 患者与健康个体的转录组测序,研究了 lncRNA 的表达谱。

结果

从 PTB 患者中筛选出 449 个差异表达(DE)(倍数变化≥2,错误发现率≤0.05)的 lncRNA。lnc-HNRNPU-1:7 和 lnc-FAM76B-4:1 是 PTB 患者中上调最明显的 lncRNA 和下调最明显的 lncRNA。GO 注释和 KEGG 分析用于探讨这些 DE lncRNA 的潜在作用。与 PTB 发病机制相关的 JAK/STAT 和 TGF-β信号通路在 PTB 患者中富集。cis 调控基因分析显示了一些 lncRNA 和 mRNA 在染色体上的共表达。Trans 分析表明 STAT1、STAT2 和 TAF7 转录因子调节 lncRNA 和 mRNA 的表达。构建的 lncRNA ceRNA 网络表明,lncRNA 可能通过海绵 miRNA 调节 mRNA 的表达。

结论

我们全面分析了 PTB 患者中 lncRNA 的表达谱,为探索失调 lncRNA 在 PTB 发病机制中的调控机制提供了新线索。

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