Overexpression of miR‑375 reverses the effects of dexamethasone on the viability, migration, invasion and apoptosis of human airway epithelial cells by targeting DUSP6

Zheng,Xiaojing; Li,Chunlian; Gao,Xiang

doi:10.3892/ijmm.2022.5081

Overexpression of miR‑375 reverses the effects of dexamethasone on the viability, migration, invasion and apoptosis of human airway epithelial cells by targeting DUSP6

Authors:
- Xiaojing Zheng
- Chunlian Li
- Xiang Gao
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Affiliations: Department of Pediatrics, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, P.R. China, Department of Cardiology, Fangzi District People's Hospital, Weifang, Shandong 261206, P.R. China
Published online on: January 5, 2022 https://doi.org/10.3892/ijmm.2022.5081
Article Number: 26
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Airway epithelial cell (AEC) dysfunction has been proven to be involved in the pathogenesis of asthma, which may be induced by the use of dexamethasone (Dex). The altered expression of microRNAs (miRNAs/miRs) has been found in asthma. However, the detailed mechanisms responsible for the effects of miR‑375 on Dex‑induced AEC dysfunction remain elusive. Thus, the present study aimed to elucidate these mechanisms. Following treatment with Dex for 0, 6, 12 and 24 h, AEC viability, migration, invasion and apoptosis were examined using Cell Counting Kit‑8 (CCK‑8), wound healing and Transwell assays, and flow cytometry, respectively. The expression levels of miR‑375, dual specificity phosphatase 6 (DUSP6) and apoptosis‑related proteins (Bcl‑2, Bax, cleaved caspase‑3) were measured using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The target genes and potential binding sites of miR‑375 and DUSP6 were predicted using TargetScan and confirmed using dual‑luciferase reporter assay. The viability, migration, invasion and apoptosis of Dex‑treated AECs were further assessed with or without miR‑375 and DUSP6. In the AECs (9HTE cells), Dex treatment suppressed cell viability and miR‑375 expression, whereas it promoted cell apoptosis and the expression of DUSP6, the target gene of miR‑375. The overexpression of miR‑375 reversed the effects of Dex treatment on miR‑375 expression, cell viability, migration and invasion, and apoptosis‑related protein expression; in turn, these effects were reversed by the overexpression of DUSP6, with the exception of miR‑375 expression. On the whole, the present study demonstrates that the overexpression of miR‑375 counteracts the effects of Dex treatment on AEC viability, migration, invasion and apoptosis by targeting DUSP6. Thus, it was suggested that the downregulated expression of miR‑375 may be a therapeutic target for AEC dysfunction.

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