MiR-203a-3p regulates TGF-β1-induced epithelial–mesenchymal transition (EMT) in asthma by regulating Smad3 pathway through SIX1

Abstract

Asthma is a common chronic airway disease with increasing prevalence. MicroRNAs act as vital regulators in cell progressions and have been identified to play crucial roles in asthma. The objective of the present study is to clarify the molecular mechanism of miR-203a-3p in the development of asthma. The expression of miR-203a-3p and Sine oculis homeobox homolog 1 (SIX1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of SIX1, fibronectin, E-cadherin, vimentin, phosphorylated-drosophila mothers against decapentaplegic 3 (p-Smad3) and Smad3 were measured by Western blot. The interaction between miR-203a-3p and SIX1 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. MiR-203a-3p was down-regulated and SIX1 was up-regulated in asthma serums, respectively. Transforming growth factor-β1 (TGF-β1) treatment induced the reduction of miR-203a-3p and the enhancement of SIX1 in BEAS-2B and 16HBE cells in a time-dependent manner. Subsequently, functional experiments showed the promotion of epithelial–mesenchymal transition (EMT) induced by TGF-β1 treatment could be reversed by miR-203a-3p re-expression or SIX1 deletion in BEAS-2B and 16HBE cells. SIX1 was identified as a target of miR-203a-3p and negatively regulated by miR-203a-3p. Then rescue assay indicated that overexpressed miR-203a-3p ameliorated TGF-β1 induced EMT by regulating SIX1 in BEAS-2B and 16HBE cells. Moreover, miR-203a-3p/SIX1 axis regulated TGF-β1 mediated EMT process in bronchial epithelial cells through phosphorylating Smad3. These results demonstrated that MiR-203a-3p modulated TGF-β1-induced EMT in asthma by regulating Smad3 pathway through targeting SIX1.

RETRACTED: MiR-1236-3p Inhibits the Proliferation, Invasion, and Migration of Colon Cancer Cells and Hinders Epithelial-Mesenchymal Transition by Targeting DCLK3

“…It was also reported that miRNAs involved in regulating the proliferation, promotion, invasion and metastasis of tumor cells (9). Furthermore, miRNAs are somehow involved in Epithelialmesenchymal Transition (EMT), which is a significant indicator of the tumor metastatic process (10). Although the importance of miRNAs in tumor progression has been explored extensively, the pathological relevance and significance of miRNAs in colon cancer remain unclear.…”

The Role of Defective Epithelial Barriers in Allergic Lung Disease and Asthma Development

“…133,134 Orosomucoid-like 3 (ORMDL3), was shown to play an important role in regulating epithelial barrier function in allergic asthma, [135][136][137] rhinovirus infection 138,139 and by inducing the p-ERK/MMP-9 pathway to promote pathological airway remodeling in patients with asthma. 140 SMAD3 is an essential signal transducer in TGF-β signaling, which is elevated in airway epithelial cells of some asthmatics 141,142 and is involved in the response of bronchial epithelial cells to viral infection. 143,144 Deletion of P2Y13 in human airway epithelial cells and in a mouse model protects against asthma exacerbations.…”

Research progress of icariin, an extract of traditional Chinese medicine, in the treatment of asthma

“…50,51 Studies have shown that TGF-β1 can regulate the miR-203a-3p/SIX1 signaling pathway to regulate the Smad3 pathway and promote the occurrence of epithelial-mesenchymal transition in asthma. 52 In vivo and in vitro experiments have found that icariin can significantly inhibit the phosphorylation of cytokines such as Erk, JNK, and p38; inhibit the activation of Smad and MAPK signaling pathways; and reduce the EMT process induced by TGF-β1 to improve airway remodeling. 53 proteins and reactive oxygen species (ROS), and cell endoplasmic reticulum dysfunction, stimulating the unfolded protein response (UPR), aggravating endoplasmic reticulum stress, airway inflammation, and airway remodeling processes.…”