Serum Exosomal microRNA Profiling in AIDS Complicated with Talaromyces marneffei Infection.

ABSTRACT

INTRODUCTION: In order to find the early diagnostic markers of AIDS combined with TM infection, we detected and analyzed the serum exosomal miRNAs of AIDS patients with or without TM infection. MATERIALS AND METHODS: We profiled the expression levels of miRNAs via RNA sequencing in serum exosomes from the pooled samples of 17 AIDS patients combined without TM infection and 15 AIDS combined with TM infection patients. For external validation, we validated these results using real-time quantification polymerase chain reaction (qRT-PCR) in an independent cohort of 35 AIDS patients combined without TM infection and 33 AIDS combined with TM infection patients. Finally, bioinformatics was used to predict the target genes and pathways of meaningful miRNAs. RESULTS: A total of 131 serum exosomal miRNAs including 73 up-regulated and 59 down-regulated miRNAs were found to be differentially expressed (log2FC≥1 and FDR <0.01) in the two groups. A validation analysis revealed that three miRNAs (miR-192-5p, miR-194-5p and miR-1246) were upregulated in exosomes from AIDS combined with TM infection patients. ROC analyses showed that the AUC in combined diagnosis of the three miRNAs was 0.742, and the diagnostic sensitivity and specificity were 0.568 and 0.861, respectively. In the biological process analysis, all the 3 miRNAs were involved in transcription, DNA-templated and positive regulation of transcription from RNA polymerase II promoter. At the same time, the related pathways were involved in TGF-ß signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc. CONCLUSION: miR-192-5p, miR-194-5p and miR-1246 in serum exosomes might be a potential biomarker for AIDS combined with TM infection patients, which may be involved in TGF-ß signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc. Further research is needed on the biological functions and mechanisms of these miRNAs.