Differential expression of miRNAs in bronchoalveolar lavage fluid and plasma from patients with chronic obstructive pulmonary disease

Abstract

Micro RNAs (MiRNAs) act as a key regulator participating in various biological process, and the roles of that play in chronic obstructive pulmonary disease (COPD) are discovered. However, recent pharmacological treatment for COPD focus on alleviating symptoms and reducing the risk events. The heterogeneous COPD causes variable responses to pharmacological interventions. COPD treatment has gradually developed into precision medicine, integrating clinical and biomarker information to optimize personalized therapy. Thus, targeting miRNAs represents a promising strategy for COPD individual therapy. Twelve COPD patients, 7 community-acquired pneumonia and 4 normal people were recruited. Total RNAs were collected from the bronch alveolar lavage cells and peripheral blood plasma of each participant. miRNAs were profiled by microarray and systematically compared between patients with different groups. Bioinformatic analysis identified pathways relevant to the pathogenesis of COPD. Next, the target pathway networks were mapped. Compared different groups, we obtain differential expression of miRNAs (Q value (Adjusted P value) < .05 and |log 2 FC| >2). Gene ontology enrichment analyses showed that differentially expressed miRNAs function as regulators in different modules of cellular component, molecular function and biological process. Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that signals, such as MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway and oxidative stress may participate in the pathogenesis of COPD. In the miRNAs target pathway networks, novel-hsa-miR26-3p or hsa-miR-3529-3p/CDC42/MAPK signaling pathway may play a role in regulating COPD. Our findings demonstrate critical roles of the miRNAs in COPD molecular pathology. The data support a plausible mechanism that miRNAs may be involved in the development of COPD by affecting the inflammatory and oxidative stress. Moreover, hsa-miR-4748/CDC42/MAPK signaling pathway may contribute to the pathogenesis of COPD, providing a potential novel therapeutic strategy in COPD.Abbreviations: BALF = bronchoalveolar lavage fluid, CAP = community-acquired pneumonia, COPD = chronic obstructive pulmonary disease, DEGS = differential expressed genes, DEmiRNAs = differential expressed miRNAs, GO = gene ontology, KEGG = Kyoto encyclopedia of genes and genomes, MiRNAs = micro RNAs, PHLPP2 = PH domain and leucine rich repeat protein phosphatases 2, RNA = ribonucleic acid，WHO = World health organization.

Immunoactive signatures of circulating tRNA- and rRNA-derived RNAs in chronic obstructive pulmonary disease

“…Circulating RNAs have emerged as novel biomarkers and functional molecules in diverse areas of disease studies. While previous investigations into circulating sncRNAs in the biofluids of COPD patients have primarily focused on miRNAs through the use of standard RNA-seq [25][26][27][28] , it is important to note that the majority of extracellular sncRNAs contain either a cP or 3′-P 24 and are thus not captured by standard RNA-seq. Moreover, even a single cP-containing tRNA half, rRF, or mRF species can be significantly more abundant than total miRNAs in tissues 30 and EVs 24 .…”

“…The copyright holder for this preprint this version posted June 19, 2024. ; https://doi.org/10.1101/2024.06. 19.599707 doi: bioRxiv preprint relied on standard RNA-seq without T4 PNK treatment [25][26][27][28] , thus focusing mainly on miRNAs.…”

“…We herein report a comprehensive characterization of circulating sncRNAs in plasma from patients with COPD. Previous investigations of circulating sncRNA expression in COPD patients relied on standard RNA-seq without T4 PNK treatment 25–28 , thus focusing mainly on miRNAs. By conducting sncRNA sequencing on plasma RNA samples pre-treated with T4 PNK, we have established the expression profile of plasma sncRNAs and their alterations between healthy individuals and COPD patients.…”

“…We herein report a comprehensive characterization of circulating sncRNAs in plasma from patients with COPD. Previous investigations of circulating sncRNA expression in COPD patients relied on standard RNA-seq without T4 PNK treatment [25][26][27][28] , thus focusing mainly on miRNAs.…”