Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer.
Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer.
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发表时间：
2015-09
影响因子：
5.3
通讯作者：
Y. Tsukamoto;S. Fumoto;T. Noguchi;K. Yanagihara;Y. Hirashita;C. Nakada;N. Hijiya;T. Uchida;K. Matsuura;R. Hamanaka;K. Murakami;M. Seto;M. Inomata;M. Moriyama
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作者：
Y. Tsukamoto;S. Fumoto;T. Noguchi;K. Yanagihara;Y. Hirashita;C. Nakada;N. Hijiya;T. Uchida;K. Matsuura;R. Hamanaka;K. Murakami;M. Seto;M. Inomata;M. Moriyama
以前，我们已经报道，在染色体20 q13的增益是最常见的基因组拷贝数畸变在胃癌（GC）（29/30例），并在位于该区域的基因，我们已经确定了DDX 27，其表达水平显示出最高的相关性与基因组拷贝数，作为一个候选的治疗靶点GC。在这里，我们分析了DDX 27的临床病理意义，使用免疫组化和研究其功能，使用敲低试验。我们发现DDX 27在胃癌组织中频繁上调（98/140例，70%），并与静脉浸润和肝转移显著相关。此外，多因素分析显示，胃癌患者中DDX 27的高表达与较差的预后独立相关。在功能测定中，敲除DDX 27降低了GC细胞在常规平板和软琼脂上形成集落的能力，但对其侵袭力几乎没有影响。我们还发现，敲低DDX 27通过抑制细胞周期进程而不依赖于细胞凋亡，从而降低GC细胞的活力。有趣的是，DDX 27消耗诱导TP 53在TP 53野生型细胞系AGS中的积累，但在TP 53缺失的细胞系44 As 3中没有，尽管DDX 27敲低通常降低两者的活力，表明DDX 27的TP 53依赖性和独立性细胞周期控制。因此，我们的研究结果表明，DDX 27的表达有助于通过细胞周期控制GC细胞的集落形成，并可能成为20 q13染色体获得的GC患者的潜在治疗靶点。
Previously, we have reported that gain at chromosome 20q13 is the most common genomic copy number aberration in gastric cancer (GC) (29/30 cases), and that among the genes located in this region, we have identified DDX27, whose expression level shows the highest correlation with genomic copy number, as a candidate therapeutic target for GC. Here, we analyzed the clinicopathological significance of DDX27 using immunohistochemistry and studied its functions using knockdown assays. We found that DDX27 was frequently upregulated in GC tissues (98 of 140 cases, 70%), and significantly associated with venous invasion and liver metastasis. Furthermore, multivariate analysis of GC patients showed that high expression of DDX27 was independently associated with poorer prognosis. In functional assays, knockdown of DDX27 reduced the ability of GC cells to form colonies both on conventional plates and soft agar, but had little effect on their invasiveness. We also found that knockdown of DDX27 reduced the viability of GC cells through inhibition of cell cycle progression independently of apoptosis. Interestingly, DDX27 depletion induced accumulation of TP53 in a TP53 wild-type cell line, AGS, but not in a TP53-deleted cell line, 44As3, although DDX27 knockdown commonly reduced the viability of both, indicating the TP53-dependent and independent cell cycle control of DDX27. Thus, our results suggest that expression of DDX27 contributes to colony formation by GC cells through cell cycle control and may be a potential therapeutic target for GC patients with chromosome gain at 20q13.