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Mechanism of epithelial-mesenchymal transition inhibited by miR-203 in non-small cell lung cancer
The aim of the present study was to investigate whether miR-203 can inhibit transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT), and the migration and invasion ability of non-small cell lung cancer (NSCLC) cells by targeting SMAD3. In the present study, the expressio...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6967097/ https://www.ncbi.nlm.nih.gov/pubmed/31894278 http://dx.doi.org/10.3892/or.2019.7433 |
Sumario: | The aim of the present study was to investigate whether miR-203 can inhibit transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT), and the migration and invasion ability of non-small cell lung cancer (NSCLC) cells by targeting SMAD3. In the present study, the expression levels of miR-203, SMAD3 mRNA and protein in NSCLC tissues were examined, as well as their corresponding paracancerous samples. The miR-203 mimics and miR-203 inhibitor were transfected into the H226 cell line. RT-qPCR was used to assess the expression levels of E-cadherin, Snail, N-cadherin and vimentin mRNA, and western blotting was performed to detect the expression levels of p-SMAD2, SMAD2, p-SMAD3, SMAD3 and SMAD4. The cell migration and invasion abilities were detected by Transwell assays. The target site of SMAD3 was predicted by the combined action between miR-203 and dual luciferase. The results revealed that the RNA levels of miR-203, compared with paracancerous tissues, were decreased in NSCLC tissues, while SMAD3 mRNA and protein levels were upregulated, and miR-203 inhibited SMAD3 expression. Induction of TGF-β led to decreased E-cadherin mRNA levels, upregulation of Snail, N-cadherin and vimentin mRNA levels (P<0.05), and significant increase in cell migration and invasion, whereas transfection of miR-203 mimics reversed the aforementioned results (P<0.05). Conversely, miR-203 inhibitor could further aggravate the aforementioned results (P<0.05). Western blot results revealed that transfection of miR-203 mimics significantly reduced the protein expression of SMAD3 and p-SMAD3 (P<0.05). Furthermore, the results of the Dual-Luciferase assay revealed that miR-203 inhibited SMAD3 expression by interacting with specific regions of its 3′-UTR. Overall, a novel mechanism is revealed, in which, miR-203 can inhibit SMAD3 by interacting with specific regions of the 3′-UTR of SMAD3, thereby restraining TGF-β-induced EMT progression and migration and invasion of NSCLC cells. |
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