Research Paper Volume 13, Issue 7 pp 10535—10554

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

Yanli Yang1, , Wenshuai Xu1, , Ruo-Lan Xiang2, , Xinlun Tian1, , Kai-Feng Xu1, ,

  • 1 Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
  • 2 Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing 100191, China

Received: September 29, 2020       Accepted: March 2, 2021       Published: April 4, 2021
How to Cite

Copyright: © 2021 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


APAP: Autoimmune pulmonary alveolar proteinosis; ATG8: autophagy-related protein 8; ATG12: autophagy-related protein 12; BPs: biological processes; CCs: cellular components; ceRNA: competing endogenous RNA; CNC: coding and non-coding co-expression; DE: differentially expressed; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; MAP: mean arterial blood pressure; MFs: molecular functions; miRNAs: microRNAs; NEDD8: neuronal precursor cell-expressed developmentally downregulated protein 8; qRT-PCR: quantitative real-time polymerase chain reaction; SPs: surfactant proteins; Ufm1: ubiquitin-fold modifier 1; Urm1: ubiquitin-related modifier 1.