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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)

Submitter: 田中 伸哉

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