Proteomic signatures corresponding to the SS18/SSX fusion gene in synovial sarcoma.
Proteomic signatures corresponding to the SS18/SSX fusion gene in synovial sarcoma.
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DOI：
10.18632/oncotarget.26493
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发表时间：
2018-12-25
期刊：
影响因子：
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通讯作者：
Saito, Tsuyoshi
中科院分区：
文献类型：
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作者：
Ishii, Midori;Suehara, Yoshiyuki;Saito, Tsuyoshi
滑膜肉瘤（SS）是一种恶性软组织病变，最常见于年轻人。染色体易位t（X; 18）（p11; q11）通过18号染色体上的SS 18基因与位于X染色体上的SSX 1、SSX 2或SSX 4基因的基因融合而导致SS 18/SSX的形成，这在超过95%的SS中被检测到。虽然多方面的证据表明SS 18/SSX融合是该肿瘤中的癌基因，但与SS 18/SSX相关的蛋白表达谱尚未阐明。在这项研究中，我们进行了蛋白质组学研究，利用SS 18/SSX敲低在三个SS细胞系，以确定与SS 18/SSX在SS中的调节蛋白。用于相对和绝对定量（i-TRAQ）分析的同量异位素标签在每个SS细胞系中鉴定了大约1700- 2，000种由SS 18/SSX融合体调节的蛋白质。我们还分析了这三种谱，以确定在所有3种细胞系中发生类似改变的蛋白质，并发现17种一致上调和18种一致下调的蛋白质，包括TAGLN和ACTN 4。此外，网络分析确定了几个关键途径，包括RUNX 2和SMARCA 4。RUNX 2和SMARCA 4在这些识别的通路中具有最高的排名。此外，我们发现TAGLN的表达抑制SS细胞系中的细胞活力。我们的数据表明，SS 18/SSX诱导的蛋白质可能促进SS的分化和细胞生长。我们相信，在目前的功能分析中获得的结果将有助于提高我们对SS 18/SSX和恶性行为之间的关系的理解。
Synovial sarcoma (SS) is a malignant soft tissue lesion and most commonly arises in young adults. Chromosomal translocation t(X;18)(p11;q11) results in the formation of SS18/SSX by gene fusion of the SS18 gene on chromosome 18 to either SSX1, SSX2, or SSX4 gene located on chromosome X, which is detected in more than 95% of SSs. Although multiple lines of evidence suggest that the SS18/SSX fusion is the oncogene in this tumor, the protein expression profiles associated with SS18/SSX have yet to be elucidated. In this study, we conducted proteomic studies using SS18/SSX knockdown in three SS cell lines to identify the regulated proteins associated with SS18/SSX in SS. Isobaric tags for relative and absolute quantitation (i-TRAQ) analyses identified approximate 1700-2,000 proteins regulated by the SS18/SSX fusion in each SS cell line. We also analyzed the three profiles to identify proteins that were similarly altered in all 3 cell lines and found 17 consistently upregulated and 18 consistently downregulated proteins, including TAGLN and ACTN4. In addition, network analyses identified several critical pathways including RUNX2 and SMARCA4. RUNX2 and SMARCA4 had the highest ranking in these identified pathways. In addition, we found that expression of TAGLN inhibited cell viability in SS cell lines. Our data suggest that the differentiation and cell growth of SS may be enhanced by the identified proteins induced by SS18/SSX. We believe that the findings obtained in the present functional analyses will help to improve our understanding of the relationship between SS18/SSX and malignant behavior in SS.