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综合性遗传和基因组网络识别了与COPD和ILD相关的微RNA
Ana B Pavel1,2, Carly Garrison3, Lingqi Luo3
1Department of Medicine, Boston University School of Medicine, 72 East Concord St, Boston, MA, 02118, USA. anapavel@bu.edu.
Scientific reports
|August 11, 2023
概括
微RNAs (miRNAs) 和它们的异型 (isomiRs) 在慢性阻塞性肺病 (COPD) 和间歇性肺病 (ILD) 中发挥作用. miR-34c和一种新型异构R调节了Notch和Ras信号通路,揭示了这些肺部疾病中的分子异质性.
科学领域:
- 肺部医学 肺部医学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 慢性阻塞性肺病 (COPD) 和间歇性肺病 (ILD) 是具有显著分子异质性的复杂肺部疾病.
- 了解COPD和ILD的分子基础对于开发向疗法至关重要.
研究的目的:
- 研究microRNAs (miRNAs) 和miRNA异型 (isomiRs) 在COPD和ILD的发病过程中的作用.
- 在不同患者子组中识别关键miRNA调节器及其相关基因网络.
主要方法:
- 来自COPD,ILD和对照样本的肺组织的短RNA测序.
- 集群和整合网络分析以确定疾病特异性的分子特征.
- 基因表达和SNP微阵列用于构建遗传和表达网络.
主要成果:
- 确定了五个不同的样本子集群,其中COPD和ILD占主导地位的组与疾病严重程度相关.
- 在COPD和ILD网络中,miR-449/34家族成为关键的miRNA调节者,影响呼吸道分化基因.
- 确定了一种具有替代种子序列的新型miR-34c-5p异构R,与正规目标不同,并且能够降低Ras信号通路基因的调节.
结论:
- 这些发现突显了COPD和ILD患者群体中的分子异质性.
- MiR-34c及其新型同位素R参与调节与肺病病原体相关的关键信号通路 (Notch和Ras).
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