The transcription factor c-Jun regulates Smad4 expression by upregulating pre-miR-183 expression to promote invasion and
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The transcription factor c-Jun regulates Smad4 expression by upregulating pre-miR-183 expression to promote invasion and metastasis of esophageal squamous cell carcinomas Xiaoling Xu 1 & Lei Zheng 2 & Na Hang 2 & Guanxia Zhu 1 & Weimin Mao 3 & Yun Fan 1 & Kaiyi Tao 3 Received: 9 June 2020 / Accepted: 14 August 2020 / Editor: Tetsuji Okamoto # The Society for In Vitro Biology 2020
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 cJun 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. Keywords miR-183 . Esophageal squamous cell carcinomas . Epithelial-mesenchymal transition . Smad4
Introduction
Xiaoling Xu, Lei Zheng, and Na Hang were regarded as joint first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11626-020-00499-6) contains supplementary material, which is available to authorized users. * Kaiyi Tao [email protected] 1
Department of Medical Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou 310022, Zhejiang, China
2
Department of Breast Surgery, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou 310012, Zhejiang, China
3
Department of Thoracic Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou 310012, Zhejiang, China
According to the latest cancer data released by the American Cancer Society in 2018, the incidence of esophageal carcinoma (EC) ranked seventh (3.2%) in all malignant tumors, and total mortality ranked sixth (5.3%) (Bray et al. 2018). Esophageal adenocarcinoma (EAC) and esophageal squamous cell carcino
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