Identification of lncRNAs and Their Regulatory Relationships with mRNAs in Response to Cryptococcus neoformans Infection of THP-1 Cells.

Abstract

Aims Cryptococcosis is an invasive fungal disease that is associated with an increasing prevalence along with a very high fatality and is primarily caused by Cryptococcus. However, its mechanism to cause pathogenicity is not yet completely understood. In this study, we aim to screen the lncRNA markers in human monocytic (THP-1) cells infected by Cryptococcus neoformans (C. neoformans) through high-throughput sequencing technology and to explore its effects on biological functions. Methods We initially conducted an lncRNA microarray analysis of the THP-1 cells infected by C. neoformans and normal THP-1 cells. Based upon these data, RT-qPCR was used to verify the expressions of the selected lncRNAs and mRNAs. We then performed functional and pathway enrichment analyses. Lastly, target prediction was performed by using the lncRNA target tool which was based on the differentially expressed lncRNAs. Results We determined 81 upregulated and 96 downregulated lncRNAs using microarray. In addition, the profiling data showed 42 upregulated and 57 downregulated genes and discovered that neuroactive ligand-receptor interaction, tyrosine metabolism, and phenylalanine metabolism are extremely impaired in the regulation of C. neoformans infection. GO enrichment analysis of the 99 differentially expressed mRNAs exhibited that these modules showed different signaling pathways and biological mechanisms like protein binding and metal ion binding. Moreover, lncRNAs and mRNAs were analyzed for their coexpression relations. A qRT-PCR analysis confirmed that the expression of the top 10 differently expressed mRNA and lincRNA. The expressions of the lncRNAs after C. neoformans infection in THP-1 cells were detected by RNA-sequence, suggesting that microarray analysis could reveal lncRNAs having functional significance that might be linked with the progression of patients. Conclusion The current study analyzed the differential lncRNAs and mRNAs in C. neoformans infection and predicted the corresponding pathways and their correlations that can offer new potential insights into the mechanistic basis of this condition.