The long noncoding RNA TUG1 is required for TGF-β/TWIST1/EMT-mediated metastasis in colorectal cancer cells
| Autor: | Wei Chen, Xiu Hu, Ying Wu, Jiayan Mao, Jiayin Yu, Xuning Shen, Hao Liu, Jian Shen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research Cell biology Epithelial-Mesenchymal Transition Lung Neoplasms Colorectal cancer Immunology Mice Nude Biology Article Metastasis Cellular and Molecular Neuroscience Mice Downregulation and upregulation Cell Movement Transforming Growth Factor beta Cell Line Tumor Gene Knockdown Techniques medicine Animals Humans RNA Small Interfering lcsh:QH573-671 Cancer Regulation of gene expression Gene knockdown Mice Inbred BALB C lcsh:Cytology Twist-Related Protein 1 Nuclear Proteins medicine.disease digestive system diseases Gene Expression Regulation Neoplastic Cancer research RNA Long Noncoding Signal transduction Colorectal Neoplasms Transforming growth factor Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 11, Iss 1, Pp 1-10 (2020) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, and metastasis is the major cause of CRC-related mortality. Transforming growth factor-beta (TGF-β) has a central role not only in the regulation of the normal colon but also in the development and metastasis of CRC. However, TGF-β is not considered an ideal therapeutic target because it shows both pro-tumorigenic and anti-tumorigenic activity, depending on the tumor stage. Therefore, it is important to find a downstream signaling component of TGF-β that can be targeted to impair CRC metastasis. Here, we show that TGF-β promotes CRC migration and upregulates the expression of long-noncoding RNA Taurine Upregulated Gene 1 (TUG1). TUG1 knockdown inhibited migration, invasion, and epithelial–mesenchymal transition (EMT) of CRC cells in vitro, and reduced CRC lung metastasis in vivo. TGF-β induced metastasis, and TUG1 knockdown inhibited these effects. In addition, TGF-β could not reverse the anti-metastasis effects of TUG1 knockdown. These data demonstrate that TUG1 is a downstream molecular of TGF-β. Moreover, TWIST1 expression was increased with TGF-β treatment, and TUG1 knockdown decreased TWIST1 expression in CRC cells. TWIST1 knockdown inhibited invasion and EMT in CRC cells; these effects were not changed by simultaneous TUG1 knockdown, indicating that TWIST1 is a downstream mediator of TUG1. Moreover, TUG1 was significantly overexpressed in CRC patients. In conclusion, TGF-β promotes metastasis of CRC via a TUG1/TWIST1/EMT signaling pathway. TUG1 may be a promising drug target to inhibit TGF-β pathway activation in the treatment of CRC. |
| Databáze: | OpenAIRE |
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