Pathway Analysis of miRNA-1 and Its Expres-sion Evaluation in Donor’s Serum from HIV-Positive Individuals vs Unaffected Controls

Abstract

Background MicroRNAs (miRNAs) are non-coding RNA molecules (19-24 nucleotides) that play a major role in a wide range of biological processes through post-transcriptional regulation of gene expression. Differential expression of miRNAs has been reported in various infectious diseases such as HIV infection. The characterization of miRNA expression profiles, especially in mammalian biofluids, which are affected by intracellular processes of different parts of the body, provides a considerable insight into pathophysiological alterations associated with host-virus interactions. Therefore, based on miR-1 bioinformatics analysis in the context of potential affected signaling pathways in HIV infection, the present study aimed to profile the expression of miR-1 in donor’s serum from HIV-positive individuals vs unaffected controls in Bushehr Blood Transfusion Center. Materials and Methods: The enrichment analysis on predicted target genes for miR-1 was performed based on miRNA-related bioinformatics tools to achieve possible regulated pathways by this miRNA. Given the pathways affected by HIV infection and the involvement of miR-1 target genes in these signaling pathways, the miR-1 expression was evaluated in serum samples of 20 treated HIV-positive individuals, 10 patients with de novo HIV infection diagnosis, and 40 healthy subjects using qRT-PCR. Data were analyzed by SPSS software version 22. Results: The enrichment analysis for identified target genes of miR-1 revealed that target genes were significantly enriched (FDR <0.05) in the four pathways of thyroid hormone, cancer pathways, endocytosis, and phosphatidylinositol signaling system. In addition, a significant increase was observed in miR-1 expression level (p-value <0.05) in de novo HIV infected patients compared with healthy subjects. A significant decrease was observed in miR-1 expression level (p-value <0.0001) in treated HIV-positive individuals compared with de novo HIV infected patients, as well. Conclusion: Bioinformatics studies indicate that the predicted target genes for miR-1 belong to the pathways related to thyroid hormone, cancer, endocytosis, and phosphatidylinositol signaling system, which are impaired pathways in HIV infection. In addition, significantly altered expression in miR-1 in the serum of de novo HIV infected patients vs healthy subjects and treated HIV-positive individuals vs de novo HIV infected patients represents remarkable effects of the process of HIV infection and pathogenesis on miR-1 expression. Hence, the findings of this study indicate the potential use of miR-1 to better understand HIV pathogenesis, and subsequent therapeutic interventions by targeting miRNA.