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SS18-SSX-regulated miR-17 promotes tumor growth of synovial sarcoma by inhibiting p21WAF1/CIP1
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| Title: | SS18-SSX-regulated miR-17 promotes tumor growth of synovial sarcoma by inhibiting p21WAF1/CIP1 |
| Authors: | Minami, Yusuke Browse this author | | Kohsaka, Shinji Browse this author | | Tsuda, Masumi Browse this author →KAKEN DB | | Yachi, Kazuhiro Browse this author | | Hatori, Nobuaki Browse this author | | Tanino, Mishie Browse this author →KAKEN DB | | Kimura, Taichi Browse this author →KAKEN DB | | Nishihara, Hiroshi Browse this author →KAKEN DB | | Minami, Akio Browse this author →KAKEN DB | | Iwasaki, Norimasa Browse this author →KAKEN DB | | Tanaka, Shinya Browse this author →KAKEN DB |
| Keywords: | Cyclin-dependent kinase inhibitor p21 | | drug resistance | | hsa-mir-17 microRNA | | SS18-SSX fusion protein | | synovial sarcoma |
| Issue Date: | Sep-2014 |
| Publisher: | Wiley-Blackwell |
| Journal Title: | Cancer Science |
| Volume: | 105 |
| Issue: | 9 |
| Start Page: | 1152 |
| End Page: | 1159 |
| Publisher DOI: | 10.1111/cas.12479 |
| Abstract: | MicroRNA (miRNA) can function as tumor suppressors or oncogenes, and also as potential specific cancer biomarkers; however, there are few published studies on miRNA in synovial sarcomas, and their function remains unclear. We transfected the OncomiR miRNA Precursor Virus Library into synovial sarcoma Fuji cells followed by a colony formation assay to identify miRNAs to confer an aggressive tumorigenicity, and identified miR-17-5p from the large colonies. MiR-17 was found to be induced by a chimeric oncoprotein SS18-SSX specific for synovial sarcoma, and all examined cases of human synovial sarcoma expressed miR-17, even at high levels in several cases. Overexpression of miR-17 in synovial sarcoma cells, Fuji and HS-SYII, increased colony forming ability in addition to cell growth, but not cell motility and invasion. Tumor volume formed in mice in vivo was significantly increased by miR-17 overexpression with a marked increase of MIB-1 index. According to PicTar and Miranda algorithms, which predicted CDKN1A (p21) as a putative target of miR-17, a luciferase assay was performed and revealed that miR-17 directly targets the 3-UTR of p21 mRNA. Indeed, p21 protein level was remarkably decreased by miR-17 overexpression in a p53-independent manner. It is noteworthy that miR-17 succeeded in suppressing doxorubicin-evoked higher expression of p21 and conferred the drug resistance. Meanwhile, introduction of anti-miR-17 in Fuji and HS-SYII cells significantly decreased cell growth, consistent with rescued expression of p21. Taken together, miR-17 promotes the tumor growth of synovial sarcomas by post-transcriptional suppression of p21, which may be amenable to innovative therapeutic targeting in synovial sarcoma. |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/3.0/deed.ja |
| Type: | article |
| URI: | http://hdl.handle.net/2115/57483 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 田中 伸哉
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