MiR-30c-5p mediates inflammatory responses and promotes microglia survival by targeting eIF2α during Cryptococcus neoformans infection.

Cryptococcosis is a disease predominantly caused by Cryptococcus neoformans in China and C. neoformans is the main form that causes cryptococcal meningitis. In this study, we examined the influence of MiR-30c-5p during Cryptococcus neoformans infection. microRNAs were extracted from Cerebrospinal fluid and sera of patients. To identify pathogenic microRNAs, RNASeq were performed. The results were confirmed with quantitative real-time PCR (qRT-PCR), transient transfection of siRNAs or microRNA mimics into cultured BV2 cell, flow cytometry, immunoblotting, luciferase assay and immunohistochemistry. In this study we found that miR-30c expression was downregulated and that inflammation, apoptosis, and autophagy were activated. The overexpression of miR-30c-5p significantly inhibited inflammation and autophagic activity and decreased apoptosis, and treatment with sieIF2α resulted in a significant decrease in inflammation, apoptosis. In addition, clinical samples of cerebrospinal fluid and serum of patients with cryptococcal meningitis who have undergone standard antifungal treatment showed that the expression of miR-30c-5p was increased while that of eIF2α was decreased, which was in accordance with the in vitro experiments. These studies demonstrated that miRNA-30c-5p can inhibit inflammatory, apoptotic, and autophagic activity through the eIF2α/ATF4 pathway, and it is thus a potential target for the diagnosis, treatment, and detection of cryptococcal meningitis.