Abstract
MiR-183 is a tumor onco-miR and has been shown by our previous studies to be overexpressed in esophageal squamous cell carcinomas (ESCCs). In this study, we sought to determine the possible mechanisms of miR-183 in ESCC. In our study, cell migration and invasion, real-time PCR, Western blot, and chromatin immunoprecipitation (ChIP) assays were used to explore the mechanism of miR-183 in three ESCC cell lines. We found several potential transcription factors, including c-Jun, by bioinformatics methods. Using a ChIP assay, we identified that c-Jun binds to the promoter region of pre-miR-183 and that upregulated c-Jun expression is related to increased expression of miR-183. We found that downregulation of miR-183 significantly reduced the cell invasiveness and migration of ESCC cells, whereas upregulation of miR-183 via a mimic increased the cell migration and invasion of ESCC cells. We further discovered one direct miR-183 target gene, Smad4, which has been implicated in invasion and metastasis. Furthermore, miR-183 promoted epithelial-mesenchymal transition (EMT), which is involved in the invasion and migration of ESCC cells. Dysregulation of miR-183 has an important role in tumor growth and invasion because miR-183 targets Smad4. Therefore, suppression of miR-183 may provide a potential approach for treatment.
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Acknowledgments
Thanks to Jianguo Feng (Zhejiang Cancer Institute) for his guidance on experimental operation.
Funding
This work was supported by the grants from the National Natural Science Foundation of China (No. 81802995) and the Medical Science and Technology Project of Zhejiang Province (Nos. 2018RC020 and 2018KY024).
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Editor: Tetsuji Okamoto
Xiaoling Xu, Lei Zheng, and Na Hang were regarded as joint first authors.
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Xu, X., Zheng, L., Hang, N. et al. The transcription factor c-Jun regulates Smad4 expression by upregulating pre-miR-183 expression to promote invasion and metastasis of esophageal squamous cell carcinomas. In Vitro Cell.Dev.Biol.-Animal 56, 550–558 (2020). https://doi.org/10.1007/s11626-020-00499-6
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DOI: https://doi.org/10.1007/s11626-020-00499-6