Differential expression of microRNA profiles in peripheral blood CD14+ monocytes between latent tuberculosis infection and pulmonary tuberculosis patients

Abstract

Objective To screen differentially expressed microRNAs (miRNAs) in peripheral blood CD14+ monocytes between latent tuberculosis infection (LTBI) and pulmonary tuberculosis patients. Methods Thirty–one patients with pulmonary tuberculosis and 31 patients with LTBI were enrolled from Shenzhen Bao'an Chronic Diseases Prevent and Treatment Hospital and Shenzhen Third People's Hospital during June 2013 and February 2014. Differentially expressed miRNAs were detected by using a miRNA chip in 6 pulmonary tuberculosis patients and 6 LTBI patients (male 3, female 3), and TaqMan qPCR test was performed to verify the differentially expressed miRNAs in two groups (25 for each). Receiver operating characteristic (ROC) curve was used to evaluate the differentially expressed miRNAs in diagnosis of pulmonary tuberculosis. Target genes of differentially expressed miRNAs were forecasted using miRFocus database, and GO term and KEGG pathway annotation were performed. Results There were 40 differentially expressed miRNAs in CD14+ monocytes between LTBI and pulmonary tuberculosis patients, among which 4 had > 2–fold up–regulation and 36 had > 2–fold down–regulation in pulmonary tuberculosis patients. All differentially expressed miRNAs could be divided into two clusters. TaqMan qPCR test showed that the expression of miR–378 (up–regulated miRNA) in pulmonary tuberculosis patients was 4.17±0.25, which was significantly higher than that in LTBI patients (2.31±0.24, t=5.25, P<0.01); the expression of miR–483–5p (down–regulated miRNA) in pulmonary tuberculosis patients was 1.71±0.16, which was significantly lower than that in LTBI patients (2.97±0.15, t=5.45, P<0.01). ROC curve analysis showed that the sensitivities and specificities of miR–378 and miR–483–5p in the diagnosis of pulmonary tuberculosis were 0.76, 0.72 and 0.84, 0.76, respectively. Bioinformatic analysis showed that the target genes of miR–378 and miR–483–5p mainly involved in cell proliferation, apoptosis, antigen presentation and signal transduction. Conclusion There are significant differences in miRNA profiles in CD14+ monocytes between LTBI and pulmonary tuberculosis patients, and the expression of miR–378 and miR–483–5p may be used for the differential diagnosis of pulmonary tuberculosis from LTBI. Key words: Mycobacterium tuberculosis; Tuberculosis, pulmonary; MicroRNAs; MicroRNA–378; MicroRNA–483–5p