Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients

Abstract

Background/Aims: Dysregulated expression of circular RNAs (circRNAs) was demonstrated to be implicated in many diseases. Here, we aimed to determine circRNA profile in peripheral blood mononuclear cells (PBMCs) from active tuberculosis (TB) patients to identify novel biomarkers for TB. Methods: Expression profile of circRNAs in PBMCs from 3 active pulmonary TB patients and 3 healthy controls were analyzed by microarray assay. Six circRNAs were selected for validation using real time-quantitative PCR (qRT-PCR) in 40 TB patients and 40 control subjects. Receiver operating characteristic (ROC) curve was constructed to evaluate their values in TB diagnosis. Hsa_circRNA_001937 was chosen for further evaluation in an independent cohort consisting of 115 TB, 40 pneumonia, 40 COPD, 40 lung cancer patients and 90 control subjects. An eight-month follow up was performed in 20 newly diagnosed TB patients to investigate the expression change of hsa_circRNA_001937 after chemotherapy. Results: We revealed and confirmed that a number of circRNAs were dysregulated in TB patients. Of the six studied physio circRNAs, the levels of hsa_circRNA_001937, hsa_circRNA_009024 and hsa_ circRNA_005086 were significantly elevated and hsa_circRNA_102101, hsa_circRNA_104964 and hsa_circRNA_104296 were significantly reduced in PBMCs from TB patients as compared to healthy controls. ROC curve analysis suggested that hsa_circRNA_001937 has the largest area under the curve (AUC = 0.873, P<0.001). Hsa_circRNA_001937 was significantly increased in patients with TB compared with patients with pneumonia, COPD and lung cancer. Hsa_ circRNA_001937 was correlated with TB severity (r = 0.4053, P = 0.010) and its expression significantly decreased after treatment. Conclusion: This study identified a set of deregulated circRNAs in active TB PBMCs, our data also suggest that hsa_circRNA_001937 can be used as a potential diagnostic biomarker of TB.

Cigarette smoke extract alters genome‐wide profiles of circular RNAs and mRNAs in primary human small airway epithelial cells

“…Some circRNAs displayed stress‐specific expression patterns. For instance, 37 circRNAs were differentially expressed in peripheral blood mononuclear cells in active tuberculosis patients . In human umbilical venous endothelial cells, a significant up‐regulation of circRNAs was identified to respond to hypoxia .…”

“…For instance, 37 circRNAs were differentially expressed in peripheral blood mononuclear cells in active tuberculosis patients. 21 In human umbilical venous endothelial cells, a significant up-regulation of circRNAs was identified to respond to hypoxia. 22 Here we report, for the first time, the circRNA and mRNA transcriptome profiles of the HSAECs under stimulation of CSE.…”

Plasma Circular RNAs hsa_circ_0001953 and hsa_circ_0009024 as Diagnostic Biomarkers for Active Tuberculosis

“…Despite increasing evidence that circRNAs widely participate in human diseases exist, the role of circRNAs in TB patients is largely unknown. Our previous study revealed some circRNAs were differentially expressed in the PBMCs between TB patients and healthy controls (Huang et al, 2018 ). In this study, the differentially expressed circRNAs in the plasma of TB patients were screened in a new cohort of subjects, the roles of plasma circulating circRNAs as novel biomarkers for active TB diagnosis were also investigated.…”

Signature of circular RNAs in peripheral blood mononuclear cells from patients with active tuberculosis

“…However, the three dysregulated circRNAs were not observed in the previous findings mentioned above. 13,15,21 This F I G U R E 4 Detailed presentation of interactions between hsa_circRNA_101128 and its five potential miRNA targets. The 2D structure displayed the MRE sequence, pairing of miRNA target nucleotides and seed type.…”