Specific and novel human microRNAs are regulated as response to fungal infection

ABSTRACT: Within the last decades, invasive fungal infections have gained increasing significance. They are characterized by high mortality rates and are often caused Candida albicans and Aspergillus fumigatus. The increasing number of infections underlines the necessity for additional anti-fungal therapies, which require an extended knowledge of gene regulations during fungal infection. MicroRNAs are regulators of important cellular processes, including immune response. By analyzing their regulation and impact on target genes, novel therapeutic approaches may be developed. Here, we examine the role of microRNAs in human dendritic cells during fungal infections. Dendritic cells represent the bridge between the innate and the adaptive immune systems. Therefore, analysis of gene regulation of dendritic cells is of particular significance. By applying next-generation sequencing of small RNAs, we quantify microRNA expression in monocyte-derived dendritic cells after 6 and 12h of infection with C. albicans and A. fumigatus as well as treatment with LPS. We use two different tools and an online database to determine potential target genes. We identified 29 microRNAs that are differentially regulated after infection by the fungi or LPS. Two and five of them are specific for fungal infections after 6h and 12h, respectively. We further validated interactions of miR-132-5p and miR-212-5p with immunological relevant target genes, such as FKBP1B, KLF4, and SPN, on both RNA and protein level. Our results indicate a fine-tuning function of these microRNAs during fungal infections. Beyond that, we identified previously undiscovered microRNAs. We validated three novel microRNAs via qRT-PCR. A comparison with known microRNAs revealed possible relations with the miR-378 family and miR-1260a/b for two of them, while the third one features a unique sequence with no resemblance to known microRNAs. In summary, this study analyzes the effect of known microRNAs in dendritic cells during fungal infections and proposes novel microRNAs that could be experimentally verified.

ORGANISM(S): Homo sapiens

PROVIDER: GSE80014 | GEO | 2017/06/12

SECONDARY ACCESSION(S): PRJNA317629

REPOSITORIES: GEO