MicroRNA-186 is associated with hypoxia-inducible factor-1α expression in chronic obstructive pulmonary disease

在慢性阻塞性肺疾病中,microRNA-186与缺氧诱导因子-1α的表达相关。

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Abstract

BACKGROUND: MicroRNAs (miRNAs) are a family of small noncoding RNAs and are essential in the regulation of gene expression. Their impacts on gene expression have been reported in various diseases. The role of hypoxia-inducible factor 1 alpha (HIF-1α) in the development and progression of chronic obstructive pulmonary disease (COPD) has also been demonstrated. However, the role of microRNA-186 (miR-186) in relation to HIF in COPD is unknown. METHODS: Cell culture experiments were performed using human lung fibroblast cells (MRC-5). Cell viability was determined by MTT and flow cytometry assays. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to assess the expression levels of HIF-1α and inflammatory cytokines. Dual-luciferase reporter assays were used to reveal the correlation between miR-186 and HIF-1α. RESULTS: After miR-186 transfection, the cell lines showed reduced proliferation and increased apoptosis. After overexpression of miR-186, we found that the HIF-1α expression level was reduced in MRC-5 cells. We found that miR-186 can affect apoptosis of inflammatory fibroblasts through the regulation of HIF-1α and affect the downstream signaling pathways. CONCLUSIONS: These data suggested that miR-186 contributes to the pathogenesis of COPD and that miRNA-186 may also affect the HIF-1α-dependent lung structure maintenance program.

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