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| Title: | Trichostatin A Suppresses EGFR Expression through Induction of MicroRNA-7 in an HDAC-Independent Manner in Lapatinib-Treated Cells. |
| Authors: | Tu, Chih-Yen;Tu, Chih-Yen;Ch, Chia-Hung;Chen, Chia-Hung;Hsia, Te-Chun;Hsia, Te-Chun;Min-Hsiang, H;Hsu, Min-Hsiang;Wei, Ya-Ling;Wei, Ya-Ling;Meng-Chieh, Y;Yu, Meng-Chieh;Chen, Wen-Shu;Chen, Wen-Shu;Hsu, Ke-Wei;Hsu, Ke-Wei;Chen, Yun-Ju;Chen, Yun-Ju;黃偉謙;Huang, Wei-Chien |
| Contributors: | 生物科技學系 |
| Date: | 2014-02 |
| Issue Date: | 2014-06-04 10:15:57 (UTC+8) |
| Abstract: | Lapatinib, a dual EGFR/HER2 tyrosine kinase inhibitor, has been shown to improve the survival rate of patients with advanced HER2-positive breast cancers. However, the off-target activity of lapatinib in inducing EGFR expression without tyrosine kinase activity was demonstrated to render HER2-negative breast cancer cells more metastatic, suggesting a limitation to the therapeutic effectiveness of this dual inhibitor in HER2-heterogeneous tumors. Therefore, targeting EGFR expression may be a feasible approach to improve the anticancer efficiency of lapatinib-based therapy. Inhibition of HDAC has been previously reported to epigenetically suppress EGFR protein expression. In this study, however, our data indicated that treatment with HDAC inhibitors trichostatin A (TSA), but not suberoylanilide hydroxamic acid (SAHA) or HDAC siRNA, can attenuate both protein and mRNA expressions of EGFR in lapatinib-treated triple-negative breast cancer cells, suggesting that TSA may suppress EGFR expression independently of HDAC inhibition. Nevertheless, TSA reduced EGFR 3′UTR activity and induced the gene expression of microRNA-7, a known EGFR-targeting microRNA. Furthermore, treatment with microRNA-7 inhibitor attenuated TSA-mediated EGFR suppression. These results suggest that TSA induced microRNA-7 expression to downregulate EGFR expression in an HDAC-independent manner. |
| Relation: | JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY |
| Appears in Collections: | [生物科技學系] 期刊論文
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