Role of miRNA-181a-2-3p in cadmium-induced inflammatory responses of human bronchial epithelial cells

Abstract

Background: Inflammation is an important priming event in the pathogenesis of pulmonary diseases, including chronic obstructive pulmonary disease (COPD). Increasing evidence indicates that microRNAs (miRNAs) contribute to the pathogenesis of COPD by regulating inflammatory response. Therefore, it is necessary to investigate novel molecular targets in COPD without any validation in COPD samples in airway inflammation. The aim of our study is to reveal novel miRNAs that can influence molecular targets for COPD and to examine the underlying mechanism in airway inflammation. Methods: We identified the downregulation of miR-181a-2-3p in the serum of COPD patients and further investigated the role of miR-181a-2-3p in cadmium (Cd)-induced inflammation of a human bronchial epithelial cell line (BEAS-2B) and normal human bronchial epithelial (NHBE) cells. Results: Our results showed that expression of miR-181a-2-3p was significantly decreased in Cd-treated cells and silencing of miR-181a-2-3p enhanced Cd-induced inflammatory responses and inflammasome activation. This negative regulatory effect of miR-181a-2-3p on inflammation is partly mediated by the calcium signaling pathway. Furthermore, global gene expression profiling revealed that Toll-like receptor 4 or sequestosome 1 genes were identified as potential targets of miR-181a-2-3p, which were significantly upregulated by knockdown of miR-181a-2-3p in Cd-treated cells. Conclusions: Our results strongly suggest that miR-181a-2-3p has a critical role in Cd-induced inflammation of airway by regulating its potential target genes, which could be molecular targets for COPD.

The noncoding and coding transcriptional landscape of the peripheral immune response in patients with COVID‐19

“…Among the miRNAs downregulated in severe cases was miR‐181a‐2‐3p, a serum biomarker of chronic obstructive pulmonary disease 31 . Downregulation of miR‐181a‐2‐3p is also associated with enhanced TLR4 and CXCL8 expression 32,33 (Figure 2H).…”

“…Among the miRNAs downregulated in severe cases was miR-181a-2-3p, a serum biomarker of chronic obstructive pulmonary disease. 31 Downregulation of miR-181a-2-3p is also associated with enhanced TLR4 and CXCL8 expression 32,33 (Figure 2H). Another downregulated miRNA was miR-99a-5p targeting the proinflammatory genes, insulin like growth factor 1 receptor (IGF1R) 34,35 and myotubularin-related protein 3 (MTMR3), which were reported to induce weaker antiviral immunity 36,37 ( Figure 2I).…”

Micro-RNAs: Crossroads between the Exposure to Environmental Particulate Pollution and the Obstructive Pulmonary Disease

“…Global gene expression profiling allowed the identification of miR-181a-2-3p targets involved in Cd-induced inflammatory responses in human bronchial epithelial cells. In particular, the authors demonstrated the involvement of the Toll-like receptor 4 ( TLR4 ), which is a fine sensor influencing inflammatory cascade by stimulation of pro-inflammatory molecules [ 136 , 137 ]. These data evidenced the role of miR-181a-2-3p and its target TLR4 in the regulation of inflammatory response in bronchial cells upon Cd exposure and their potential role in COPD pathophysiology.…”

Long non‑coding maternally expressed gene 3 regulates cigarette smoke extract‑induced apoptosis, inflammation and cytotoxicity by sponging miR‑181a‑2‑3p in 16HBE cells

“…The results of the present study may provide a promising avenue for treatment of COPD. 19). These participants (no other diseases) did not receive chemotherapy, radiotherapy or other therapy prior to blood collection.…”