Circulating microRNAs as biomarkers for the early diagnosis of childhood tuberculosis infection

Abstract

MicroRNAs (miRNAs) are a class of highly conserved, single-stranded RNA molecules (length, 18-25 nt) that regulate the expression of their target mRNAs. Previous studies have demonstrated that miRNAs may be novel biomarkers in the diagnosis of certain diseases. In order to evaluate the diagnostic value of miRNAs in childhood tuberculosis (TB), the circulating miRNA profile was determined using microarray analysis. An miRNA-gene network was constructed to identify closely associated miRNAs and these miRNAs were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A receiver operational curve (ROC) was used to evaluate the diagnostic sensitivity and specificity of confirmed miRNAs. The microarray data demonstrated that 29 miRNAs were altered with 15 upregulated and 14 downregulated. The network showed indicated 14 miRNAs that are critical in childhood TB. RT-qPCR validated that MIR-1, MIR-155, MIR-31, MIR-146a, MIR-10a, MIR-125b and MIR-150 were downregulated in while MIR-29 was upregulated in children with TB compared with uninfected children. The ROC curve data indicated the diagnostic value of single miRNA was as follows: MIR-150>miR-146a>miR-125b>miR-31>miR-10a>miR-1>miR-155>miR-29. Notably, a combination of these miRNAs exhibited increased diagnostic value compared with any single miRNA. To the best of our knowledge, the present study is the first to identify the expression profile of circulating miRNAs in childhood TB and demonstrated that miRNAs may be a novel, non-invasive and effective biomarker for the early diagnosis of childhood TB.