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Published on: January 30, 2014
MiR-30c-5p mediates inflammatory responses and promotes microglia survival by targeting eIF2α during Cryptococcus
Yi Jin1, Guotai Yao1, Yan Wang1
1Department of Dermatology, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai, 200003, China.
Abstract:
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.
Insights
MicroRNA-30c-5p plays a crucial role in cryptococcal meningitis by regulating inflammation and apoptosis. Restoring its levels may offer a new diagnostic and therapeutic strategy for this serious infection.
Area of Science:
- * Infectious Diseases
- * Molecular Biology
- * Immunology
Background:
- * Cryptococcosis, primarily caused by *Cryptococcus neoformans*, is a significant cause of meningitis in China.
- * The role of microRNAs in the pathogenesis of cryptococcal meningitis remains incompletely understood.
Purpose of the Study:
- * To investigate the role of microRNA-30c-5p (miR-30c-5p) in *Cryptococcus neoformans* infection.
- * To elucidate the underlying molecular mechanisms, including the eIF2α/ATF4 pathway.
- * To evaluate miR-30c-5p as a potential biomarker and therapeutic target for cryptococcal meningitis.
Main Methods:
- * RNA sequencing (RNASeq) of microRNAs from cerebrospinal fluid and serum of patients.
- * Quantitative real-time PCR (qRT-PCR) for validation.
- * In vitro experiments using cell cultures (BV2 cells) with siRNA/microRNA mimics, flow cytometry, immunoblotting, luciferase assays, and immunohistochemistry.
- * Analysis of clinical samples from patients with cryptococcal meningitis.
Main Results:
- * miR-30c-5p expression was significantly downregulated during *Cryptococcus neoformans* infection, correlating with activated inflammation, apoptosis, and autophagy.
- * Overexpression of miR-30c-5p suppressed inflammation, autophagy, and apoptosis in vitro.
- * Inhibition of eIF2α reduced inflammation and apoptosis.
- * Clinical data showed increased miR-30c-5p and decreased eIF2α expression after antifungal treatment, consistent with in vitro findings.
Conclusions:
- * miR-30c-5p acts as a negative regulator of inflammatory, apoptotic, and autophagic responses in cryptococcal meningitis via the eIF2α/ATF4 pathway.
- * miR-30c-5p represents a promising diagnostic and therapeutic target for cryptococcal meningitis.

