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自身免疫性肺泡蛋白沉积症患者中长链非编码 RNA 和 mRNAs 的表达谱及潜在功能。

Expression profiles and potential functions of long noncoding RNAs and mRNAs in autoimmune pulmonary alveolar proteinosis patients.

机构信息

Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing 100191, China.

出版信息

Aging (Albany NY). 2021 Apr 4;13(7):10535-10554. doi: 10.18632/aging.202818.

Abstract

Autoimmune pulmonary alveolar proteinosis (APAP) is a rare lung disease that may be associated with surfactant overaccumulation. To assess the function of long noncoding RNAs (lncRNAs) in APAP, we performed microarray analyses to identify differentially expressed (DE) lncRNAs and mRNAs between peripheral blood samples from five APAP patients and five healthy volunteers. In total, 12459 DE lncRNAs and 9331 DE mRNAs were identified in APAP patient samples. A qRT-PCR validation of 20 DE lncRNAs and 20 mRNAs indicated that 12 DE lncRNAs may be involved in the pathogenesis of APAP. Coding and noncoding co-expression (CNC) and competing endogenous RNA (ceRNA) regulatory networks were constructed with these 12 DE lncRNAs. Gene Ontology analysis of the downregulated mRNAs and the CNC network revealed that "ubiquitin-like protein transferase activity" was suppressed in APAP patient samples. Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that the "MAPK signaling pathway" was enriched in the ceRNA network. Gene Ontology analysis also indicated that mRNAs involved in many transmembrane ion transport processes were upregulated in APAP patients. The DE lncRNAs and mRNAs discovered in this study have elucidated the pathogenesis of APAP, and the CNC and ceRNA networks have provided novel insights for future functional research.

摘要

自身免疫性肺性肺泡蛋白沉积症(APAP)是一种罕见的肺部疾病,可能与表面活性剂过度积累有关。为了评估长链非编码 RNA(lncRNA)在 APAP 中的功能,我们进行了微阵列分析,以鉴定来自 5 名 APAP 患者和 5 名健康志愿者的外周血样本中的差异表达(DE)lncRNA 和 mRNA。在 APAP 患者样本中,共鉴定出 12459 个 DE lncRNA 和 9331 个 DE mRNA。对 20 个 DE lncRNA 和 20 个 mRNA 的 qRT-PCR 验证表明,12 个 DE lncRNA 可能参与了 APAP 的发病机制。使用这 12 个 DE lncRNA 构建了编码和非编码共表达(CNC)和竞争内源性 RNA(ceRNA)调控网络。下调 mRNAs 和 CNC 网络的基因本体论分析表明,“泛素样蛋白转移酶活性”在 APAP 患者样本中受到抑制。京都基因与基因组百科全书分析表明,ceRNA 网络中富含“MAPK 信号通路”。基因本体论分析还表明,参与许多跨膜离子转运过程的 mRNAs 在 APAP 患者中上调。本研究中发现的 DE lncRNA 和 mRNA 阐明了 APAP 的发病机制,CNC 和 ceRNA 网络为未来的功能研究提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c34/8064141/3e0b851ac7cf/aging-13-202818-g001.jpg

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