Investigation of circulating lncRNAs as potential biomarkers in chronic respiratory diseases

Abstract

Background In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases. Methods In the discovery cohort, the gene expression level of 84 lncRNAs were measured in the blood of 24 adult patients including healthy controls and patients with asthma and COPD. In the replication cohort the expression of 6 selected lncRNAs were measured in 163 subjects including healthy controls and adults with allergic rhinitis, asthma, COPD and children with asthma. It was evaluated whether these lncRNAs can be used as diagnostic biomarkers for any studied disease. With systems biology analysis the biological functions of the selected lncRNAs were predicted. Results In the discovery cohort, the mean expression of 27 lncRNAs showed nominally significant differences in at least one comparison. OIP5-AS1, HNRNPU, RP11-325K4.3, JPX, RP11-282O18.3, MZF1-AS1 were selected for measurement in the replication cohort. Three lncRNAs (HNRNPU, RP11-325K4.3, JPX) expressed significantly higher in healthy children than in adult controls. All the mean expression level of the 6 lncRNAs differed significantly between adult allergic rhinitis patients and controls. RP11-325K4.3, HNRNPU and OIP5-AS1 expressed higher in allergic asthma than in non-allergic asthma. COPD and asthma differed in the expression of RP11-325K4.3 from each other. In examining of the lncRNAs as biomarkers the weighted accuracy (WA) values were especially high in the comparison of healthy controls and patients with allergic rhinitis. OIP5-AS1 and JPX achieved 0.98 and 0.9 WA values, respectively, and the combination of the selected lncRNAs also resulted in a high performance (WA = 0.98). Altogether, OIP5-AS1 had the highest discriminative power in case of three out of six comparisons. Conclusion Differences were detected in the expression of circulating lncRNAs in chronic respiratory diseases. Some of these differences might be utilized as biomarkers and also suggest a possible role of these lncRNAs in the pathomechanism of these diseases. The lncRNAs and the associated pathways are potential therapeutic targets in these diseases, but naturally additional studies are needed for the confirmation of these results.

Screening and Verification of Differentially Expressed Long Non-coding RNAs in the Peripheral Blood of Patients With asthma

“…Although there have been clinical trials to detect the differential expression of lncRNAs in the peripheral blood of patients with asthma ( Gál et al, 2020 ; Zheng et al, 2020 ), there are many lncRNAs that have not been annotated. Finding other lncRNAs that may play a key role in asthma is therefore important, and may contribute to a better understanding and treatment of asthma.…”

“…An increasing number of lncRNAs have been functionally annotated. Although studies have reported some differences in lncRNAs in asthma patients during both childhood ( Zheng et al, 2020 ) and adulthood ( Gál et al, 2020 ), there are many lncRNAs with an unclear relationship to asthma that require investigation and annotation. In the present study, we aimed to perform whole transcriptome sequencing in patients with asthma using second-generation high-throughput sequencing to identify dysregulated lncRNAs that are associated with asthma.…”

Long non-coding RNA OIP5-AS1 regulates smoke-related chronic obstructive pulmonary disease via targeting micro RNA -410-3p/IL-13

“…Hundreds of studies have confirmed the anomalous expression of lncRNA in lung tissue of COPD, and some lncRNA showed obvious and specific expression, which will help to find early biomarkers and drug treatment targets related to COPD. In an investigation about chronic respiratory diseases, the expression of OIP5-AS1 is elevated in COPD patients compared with patients with asthma [ 33 ]. The current study indicated that the levels of OIP5-AS1 were elevated in smokers and smokers with COPD, which provided that OIP5-AS1 may be used as an early biomarker of COPD occurrence and development.…”

Long non‐coding RNA OIP5‐AS1 (Cyrano): A context‐specific regulator of normal and disease processes

“…Previous studies have been done to determine whether lncRNAs can be used as biomarkers for chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) 77,78 . OIP5‐AS1 shows differential expression in models of asthma relative to controls, 79,80 and as such, it has been found to have discriminative power as a potential biomarker for asthma 77,79 .…”

“…Previous studies have been done to determine whether lncRNAs can be used as biomarkers for chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) 77,78 . OIP5‐AS1 shows differential expression in models of asthma relative to controls, 79,80 and as such, it has been found to have discriminative power as a potential biomarker for asthma 77,79 . Its functions in apoptosis regulation and inflammatory processes in multiple cell types, and the association of these characteristics with bronchial asthma, also justified studies of OIP5‐AS1 in asthma.…”