4-phenylbutyric acid promotes migration of gastric cancer cells by histone deacetylase inhibition-mediated IL-8 upregulation
| Autor: | Xiaonan Shi, Libao Gong, Yunpeng Liu, Kezuo Hou, Yibo Fan, Ce Li, Ti Wen, Xiujuan Qu, Xiaofang Che |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Epigenetics, Vol 15, Iss 6-7, Pp 632-645 (2020) |
| Druh dokumentu: | article |
| ISSN: | 1559-2294 1559-2308 15592294 |
| DOI: | 10.1080/15592294.2019.1700032 |
| Popis: | Histone acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). It is associated with gene transcription and expression. 4-Phenylbutyric acid (4-PBA), an HDAC inhibitor (HDACi), can inhibit cancer cell proliferation by increasing the level of histone acetylation. However, 4-PBA did not show any efficacy in clinical trials. In this study, we found that 4-PBA induced epithelial–mesenchymal transition (EMT) in gastric cancer cell lines MGC-803 and BGC-823 with ectopic E-cadherin expression. Based on the expression profile microarray, IL-8 was the most significantly up-regulated gene by 4-PBA, and was selected for further investigation. Knockdown of IL-8 partially prevented 4-PBA-induced-EMT by blocking the activation of the downstream Gab2-ERK pathway. Furthermore, CHIP assay confirmed that acetyl-H3 directly combined with the promoter region of IL-8 to promote its transcription. Therefore, the results of this study demonstrated that 4-PBA-mediated inhibition of HDAC activity could induce EMT in gastric cancer cells via acetyl-histone-mediated IL-8 upregulation, and the downstream Gab2/ERK activation. These data indicated the possible reason for the failure of 4-PBA in clinical trials. |
| Databáze: | Directory of Open Access Journals |
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