circARRDC3 contributes to interleukin‑13‑induced inflammatory cytokine and mucus production in nasal epithelial cells via the miR‑375/KLF4 axis

Wang,Tao; Wang,Peihua; Chen,Dong; Xu,Zhou; Yang,Liyun

doi:10.3892/mmr.2020.11780

circARRDC3 contributes to interleukin‑13‑induced inflammatory cytokine and mucus production in nasal epithelial cells via the miR‑375/KLF4 axis

Authors:
- Tao Wang
- Peihua Wang
- Dong Chen
- Zhou Xu
- Liyun Yang
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Affiliations: Department of Otolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, P.R. China
Published online on: December 13, 2020 https://doi.org/10.3892/mmr.2020.11780
Article Number: 141
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Allergic rhinitis (AR) is a common inflammatory disorder of the nasal mucosa. It is a major risk factor for asthma development, and uncontrolled AR can lead to the worsening of asthma symptoms, which affects the quality of life and productivity of patients. Circular RNAs (circRNA) were reported to be involved in the pathogenesis of AR. The aim of the present study was to investigate the functional role of circRNA arrestin domain‑containing 3 (circARRDC3) in AR progression. circARRDC3 knockdown suppressed the levels of granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) and eotaxin and mucin 5AC (MUC5AC) in IL‑13‑induced nasal epithelial cells. Moreover, circARRDC3 silencing promoted viability and suppressed apoptosis in IL‑13‑induced NECs. circARRDC3 targeted microRNA (miR)‑375 and negatively regulated its expression. miR‑375 inhibition reversed the effects of circARRDC3 knockdown on GM‑CSF, eotaxin and MUC5AC expression levels, cell viability and cell apoptosis. In addition, miR‑375 inhibited krueppel‑like factor 4 (KLF4) expression through direct interaction, and miR‑375 overexpression inhibited GM‑CSF, eotaxin and MUC5AC expression levels, and cell apoptosis, which was abolished following KLF4 overexpression. In addition, circARRDC3, miR‑375 and KLF4 were all dysregulated in the nasal mucosa of patients with AR. miR‑375 expression was negatively correlated with circARRDC3 and KLF4 expression, and circARRDC3 expression was positively correlated with KLF4 expression. In conclusion, circARRDC3 contributed to the development of AR by regulating the miR‑375/KLF4 axis. These findings may provide novel insights into the pathogenesis of AR.

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