Blood circRNAs as biomarkers for the diagnosis of community‐acquired pneumonia

Abstract

Circular RNAs (circRNAs) have been reported as effective diagnostic and therapeutic biomarkers in many diseases, but the potential of using this easy‐to‐monitor and highly stable materials for diagnosing Community‐acquired pneumonia (CAP) remains unexplored. Here, aiming to identify potential CAP‐related circRNAs in peripheral blood and seeking to deepen the understanding of how circRNA‐miRNA‐mRNA regulatory networks may contribute to CAP, we applied microarrays profiling analysis and identified 8296 differentially expressed (DE) circRNAs between patients with CAP (n = 6) and healthy controls (n = 6). Subsequently, we validated the accumulation trends for the top 100 DE circRNAs based on qPCR in an independent validation cohort (30 patients vs 30 controls), and ultimately identified a panel of four circRNAs that perform extremely well as sensitive and specific biomarkers for diagnosing CAP: hsa_circ_0018429 (area under the curve [AUC] = 0.8216), hsa_circ_0026579 (AUC = 0.7733), hsa_circ_0125357 (AUC = 0.7730), and hsa_circ_0099188 (AUC = 0.6978); combined as a panel (AUC = 0.8776). In addition, hsa_circ_0026579 exhibited good performance in differentiating viral from bacterial or mixed infection, with an AUC of 0.863. We also identified 10 miRNAs that most likely to interact with these four circRNAs, and then predicted 205 mRNA target genes. The KEGG pathway enrichment analysis suggested highly plausible functional implications related to inflammation and to virus‐infection‐related signaling pathways (such as HTLV‐1 infection and hepatitis B infection). Thus, we generated a genetic network of potential CAP‐related regulatory interactions that should inform future hypothesis‐driven research into the causes and potential treatment of this widespread and frequently fatal disease.

circ_VMA21 protects WI-38 cells against LPS-induced apoptotic and inflammatory injury by acting on the miR-409-3p/KLF4 axis

“…A handful of circRNAs have been revealed to participate in the regulation of pneumonia (Zhao et al 2019;Zhong et al 2019). For instance, Jia et al (2020) stated that circ_406961 inhibited the particulate matter (PM)-induced inflammatory response in human bronchial epithelial 16HBE cells by interacting with ILF2 and activating the STAT3/JNK pathway.…”

Hsa_circularRNA_0079201 suppresses chondrocyte proliferation and endochondral ossification by regulating the microRNA‑140‑3p/SMAD2 signaling pathway in idiopathic short stature

“…Upregulated hsa_circ_0089172 expression was confirmed using RT-qPCR, whilst in vitro experiments revealed that hsa_circ_0089172 could be a potential diagnostic biomarker, as it plays a crucial role in the pathogenesis of Hashimoto's thyroiditis by sponging miR-125a-3p. Zhao et al ( 37 ), Qian et al ( 38 ) and Wang et al ( 39 ) assessed differences in the circRNA expression level of peripheral blood samples from patients with community-acquired pneumonia, active pulmonary tuberculosis, and in patients who were small for their gestational age, respectively, with their results suggesting that circRNAs could be reliable biomarkers for diagnosing these conditions. Notably, to the best of our knowledge, the effects of aberrant circRNA expression on ISS has not been investigated, even though an increasing number of studies have investigated the functions of circRNAs in diseases ( 34 - 39 ).…”

The Expression Profiles and Role of Circular RNA in Peripheral Blood of Myocardial Infarction Patients

“…Early diagnosis can guide clinical medication to effectively treat MI and signi cantly improved their prognosis. circRNAs have already been con rmed as effective biomarkers for numerous diseases, such as cancer [33], acquired pneumonia [34], Kawasaki disease [35]. It was reported that hsa_circ_0004104 was upregulated in coronary artery disease (CAD), and its overexpression might contribute to the pathogenesis of CAD [36].…”