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.

Microbial Pathogenesis
|January 21, 2020
PubMed

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.

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