Integrated analysis of miRNA and transcription factor gene expression profiles associated with anti-tuberculosis treatment responses
摘要
Tuberculosis (TB) is a severe respiratory illness that can lead to opportunistic infections in individuals with weakened immune systems. Accurate diagnosis and monitoring of treatment responses are essential. In this study, we analyzed the miRNA and mRNA profiles of 12 patients with active TB (ATB) before and after treatment.
MethodsWe identified differentially expressed (DE) microRNAs (miRNAs) and messenger RNAs (mRNAs), and investigated the relationship between the expression of miRNAs and their target mRNAs. We validated the selected miRNA levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR).
ResultsAfter six months of treatment, miRNA profiling of patients with ATB revealed nine miRNAs with altered expression levels. Anti-TB treatment restored miR-223-3p, miR-6787-3p, miR-338-5p, miR-1273h-3p, miR-1288-3p, miR-200c-3p, miR-3074-3p, miR-433-3p, and miR-200b-3p levels to those observed in healthy controls. We conducted qRT-PCR to verify the top nine DE miRNAs using an additional set of 22 blood samples. The results showed that all nine DE miRNAs exhibited decreased expression after the completion of therapy. mRNA sequencing was performed on the same blood samples. This analysis confirmed the significant DE of 75 mRNAs, of which 13 (AFF3, NT5C1B, HIC2, SPATA25, ZFYVE9, HTR7, LRRC8E, METTL2A, PLD4, RGS5, EME2, TIGD5, and PEG10) interacted with the miRNAs pre-analyzed using the miRWalk miRNA target prediction and analysis program.
ConclusionThe DE miRNAs identified in this study may serve as potential biomarkers for monitoring the therapeutic efficacy of ATB.
Clinical trial numberNot applicable.