SS18-SSX-regulated miR-17 promotes tumor growth of synovial sarcoma by inhibiting p21WAF1/CIP1.
SS18-SSX-regulated miR-17 promotes tumor growth of synovial sarcoma by inhibiting p21WAF1/CIP1.
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DOI：
10.1111/cas.12479
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发表时间：
2014-09
期刊：
影响因子：
5.7
通讯作者：
Tanaka S
中科院分区：
文献类型：
--
作者：
Minami Y;Kohsaka S;Tsuda M;Yachi K;Hatori N;Tanino M;Kimura T;Nishihara H;Minami A;Iwasaki N;Tanaka S
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.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
DOI：
10.1073/pnas.0800121105
发表时间：
2008-04-01
影响因子：
11.1
作者：
Calin, George A.;Cimmino, Amelia;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
DOI：
10.1073/pnas.0804549105
发表时间：
2008-07-29
影响因子：
11.1
作者：
Mitchell, Patrick S.;Parkin, Rachael K.;Tewari, Muneesh
通讯作者：
Tewari, Muneesh
影响因子：
3.6
作者：
Peng, Chang-Liang;Guo, Wei;Tang, Xiao-Dong
通讯作者：
Tang, Xiao-Dong
影响因子：
11.2
作者：
Ota, A;Tagawa, H;Seto, M
通讯作者：
Seto, M