Background: ICG-001, an antagonist of CBP (CREB-binding protein), has been demonstrated to exert anti-tumor activity via the modulation of the Wnt signalling pathway. It has previously been demonstrated that miRNAs play an important role in ICG-001-mediated tumor suppression. In the present study, the role of miRNA-134 and 1-integrin in ICG-001-mediated anti-tumor activity in nasopharyngeal carcinoma (NPC) was examined. Methods: NPC cell lines including C666-1, HONE-1 and HK-1 were used in this study. RT-PCR and Western blot were used to study the expression of miRNA-134 and the protein expression of the target proteins, respectively. Confocal microscopy was used to analyse the subcellular localization of 1-integrin. In the functional studies, in vitro endothelial adhesion assay and in vivo nude mice model were used to evaluate the adhesion and migration of ICG-001-treated NPC cells in animals, respectively. Results: ICG-001 was found to up-regulate the expression of miRNA-134 and down-regulate 1-integrin in NPC cells. The effect was accompanied with the inhibition of the adhesion of NPC cells to lung endothelial cells. In addition, over-expression of miRNA-134 would down-regulate the expression of 1-integrin. Results from 1-integrin 3'UTR Renilla luciferase reporter assay confirmed that 1-integrin is a target of miRNA-134 in NPC cells. In the animal study, the ability of ICG-001-pretreated NPC cells or stable miRNA-134 expressing NPC cells to migrate to the mouse lung was greatly reduced. Conclusion: The CBP antagonist ICG-001 may further be developed as an anti-tumor agent for the treatment of nasopharyngeal carcinoma
| Identifer | oai:union.ndltd.org:hkbu.edu.hk/oai:repository.hkbu.edu.hk:etd_oa-1882 |
| Date | 07 September 2020 |
| Creators | Chiang, Yiu Chun |
| Publisher | HKBU Institutional Repository |
| Source Sets | Hong Kong Baptist University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Open Access Theses and Dissertations |
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