MicroRNA-761 suppresses remodeling of nasal mucosa and epithelial–mesenchymal transition in mice with chronic rhinosinusitis through LCN2

Abstract

Background: Chronic rhinosinusitis (CRS) is characterized by persistent symptomatic inflammation of the nasal passage and sinus mucosa. Various microRNAs (miRs) have been implicated in CRS. Hence, the current study was conducted to explore the effect of microRNA-761 (miR-761) on remodeling of nasal mucosa and epithelial-mesenchymal transition (EMT).Methods: Bioinformatics analysis was initially performed to predict the differentially expressed genes (DEGs) associated with CRS. Gene targeting relationship between miR-761 and lipocalin 2 (LCN2) was analyzed by bioinformatics analysis and verified using dual-luciferase reporter gene assay. Histopathological analyses of the nasal mucosa tissues were conducted via hematoxylin-eosin (HE) and alcian blue (AB)-periodic acid Schiff (PAS) staining. ELISA was employed to determine the IL-8 and MMP-9 levels. To define downstream pathway of miR-761, levels of proteins related to LCN2/Twist1 signaling pathway were assessed. Additionally, the effects of miR-761 on EMT, proliferation, and apoptosis were determined.Results: LCN2 was highly expressed in CRS. LCN2 was a target of miR-761. miR-761 overexpression or LCN2 silencing decreased IL-8 and MMP-9 levels and morphological changes in nasal epithelial tissue from CRS mice. Overexpressed miR-761 or silenced LCN2 decreased the expression of LCN2 and Twist1, indicating LCN2/Twist1 signaling pathway was inactivated. Moreover, miR-761 overexpression or LCN2 silencing reduced the expression of N-cadherin and vimentin, while increased that of E-cadherin, suggesting inhibition of EMT. Furthermore, miR-761 overexpression or LCN2 silencing promoted cell proliferation and inhibited cell apoptosis in CRS.Conclusion: Taken together, miR-761 suppressed the remodeling of nasal mucosa through inhibition of LCN2 and the LCN2/Twist1 signaling pathway.

Spotlight on microRNAs in allergy and asthma

“…The importance of miRNA regulation in the pathogenesis of the aforementioned allergic diseases is supported by many studies, but also in other allergic diseases such as food allergy or chronic rhinosinusitis the evidence for a role of miRNAs is emerging. 4,10,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Figure 2 provides an overview of miRNAs in cells and tissues that are associated with allergic diseases presented herein.…”

Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression

“…Hence, it was hypothesized in the present study that if Klotho expression is a determinant of pemetrexed sensitivity, pemetrexed may suppress cell proliferation by regulating N-cadherin and Snail through the induction of LCN2. It was reported that microRNA (miR)-761 overexpression reduced the expression of N-cadherin and vimentin, but increased the expression of E-cadherin suggesting inhibition of EMT ( 52 ). Tao et al ( 53 ) demonstrated that miR-451a serves a significant role in suppressing the drug resistance of lung cancer cells treated with doxorubicin by alleviating the effect on the EMT, as evidenced by marked reductions in the expressions of N-cadherin and vimentin.…”

MicroRNA-761 modulates foam cell formation and inflammation through autophagy in the progression of atherosclerosis

“…Our interest in miR-761 is based on its effect on modulation of cardiomyocyte apoptosis and myocardial infarction [20]. Recent studies have shown that miR-761 negatively regulates the expression of the target gene lipocalin 2 (LCN2), and LCN2 silencing can suppress the expression of IL-18 and MMP9 in mice nasal mucosal epithelial tissues [35]. Another study showed that LCN2 gene also expresses in macrophages, and LCN2 can promote the secretion of inflammatory cytokines in macrophages and promote macrophages polarize into M1 phenotype [36].…”