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Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET
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| Title: | Downregulation of miRNA-31 induces taxane resistance in ovarian cancer cells through increase of receptor tyrosine kinase MET |
| Other Titles: | miRNA-31の発現低下により、レセプターチロシンキナーゼMETの抑制が解除され、卵巣癌のタキサン耐性が誘導される |
| Authors: | 三田村, 卓 Browse this author |
| Keywords: | ovarian cancer | | microRNA | | MET | | chemoresistance | | paclitaxel |
| Issue Date: | 28-Jun-2013 |
| Publisher: | Hokkaido University |
| Publisher DOI: | 10.1038/oncsis.2013.3 |
| Abstract: | Ovarian cancer is one of the most aggressive female reproductive tract tumors. Paclitaxel (PTX) is widely used for the treatment of ovarian cancer. However, ovarian cancers often acquire chemotherapeutic resistance to this agent. We investigated the mechanism of chemoresistance by analysis of microRNAs using the ovarian cancer cell line KFr13 and its PTX-resistant derivative (KFr13Tx). We found that miR-31 was downregulated in KFr13Tx cells, and that re-introduction of miR31 re-sensitized them to PTX both in vitro and in vivo. miR-31 was found to bind to the 30-UTR of mRNA of MET, and the decrease in MET correlated to higher sensitivity to PTX. Furthermore, co-treatment of KFr13Tx cells with MET inhibitors sensitized the tumor cells to PTX both in vitro and in vivo. In addition, lower levels of miR31 and higher expression of MET in human ovarian cancer specimens were significantly correlated with PTX chemoresistance and poor prognosis. This study demonstrated miR31-dependent regulation of MET for chemoresistance of ovarian cancer, raising the possibility that combination therapy with a MET inhibitor and PTX will increase PTX efficacy. |
| Description: | 雑誌に発表。Oncogenesis (2013) 2, e40; doi:10.1038/oncsis.2013.3; 共著者あり。共著者名：H Watari, L Wang, H Kanno, MK Hassan,M Miyazaki, Y Katoh, T Kimura, M Tanino, H Nishihara, S Tanaka, and N Sakuragi 配架番号：2057 |
| Conffering University: | 北海道大学 |
| Degree Report Number: | 甲第11041号 |
| Degree Level: | 博士 |
| Degree Discipline: | 医学 |
| Examination Committee Members: | (主査) 教授 大場 雄介, 教授 田中 伸哉, 教授 櫻木 範明, 准教授 濱田 淳一 |
| Degree Affiliation: | 医学研究科（病態制御学専攻） |
| Type: | theses (doctoral) |
| URI: | http://hdl.handle.net/2115/53260 |
| Appears in Collections: | 学位論文 (Theses) > 博士 （医学）
課程博士 (Doctorate by way of Advanced Course) > 医学院(Graduate School of Medicine)
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