Tuberculosis-related miRNAs have potential as disease biomarkers

Abstract

Background: More effective biomarkers for use intuberculosis prevention,diagnosis, and treatmentare urgently needed. The potential of miRNAsfor use as biomarkers of human disease has received much attention; however, suitable miRNA biomarkers for use in tuberculosis (TB) diagnosis and treatment have not yet been identified. Methods: We used human miRNA arrays to identify miRNAs in Peripheral Blood Mononuclear Cells (PBMCs) that are differentially expressed in subjects with active disease, those with latent TB infections (LTBI) and healthy individuals. The relationship between differentially-expressed miRNAs and mRNAs was examined using Tar- getScanS, Pic-Tar and miRanda. The expression profiles of selected miRNAs in subjects with active disease, those with LTBI and healthy individuals were validated by qRT-PCR. Results: miRNA array analysis of PBMCs from subjects with active disease, those with LTBI and healthy individuals identified 26 differentially-expressed miRNAs. Analysis of gene expression levels in THP-1 cells using mRNA arrays identified 87 differentially-expressed genes, 80 of which were up-regulated (ratio >2) and 7 of which were down-regulated (ratio In silico miRNA tar- get prediction identified target mRNAs for 15of the 26 differentially-expressed miRNAs. Diffe- rentially-expressed miRNAs were identified for 90 of the 178 differentially-expressed genes. has-miR-21* and has-miR-26b had the highestnumbers of differentially-expressed target mRNAs.PCR validation of has-miR-21* and has-miR- 15b* demonstrated the fidelity of our microarray results. Conclusion: Whole-genome transcrip- tional profiling identified differentially-express- ed mRNAs and miRNAs. Differentially-express- ed miRNAs combined with predicted differential- ly-expressed mRNAs from the same whole-ge- nome transcriptional profiling may be used as the new ways to better understand TB disease.This discovery of differentially-ex-pressed miRNAsand mRNAs provides a resource for further stu- dies on the role of miRNAs in tuberculosis.