SDR9C7 promotes lymph node metastases in patients with esophageal squamous cell carcinoma.

SDR9C7 promotes lymph node metastases in patients with esophageal squamous cell carcinoma.
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SDR9C7促进食管鳞状细胞癌患者的淋巴结转移

DOI:
10.1371/journal.pone.0052184
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Fan D
Fan D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tang S;Gao L;Bi Q;Xu G;Wang S;Zhao G;Chen Z;Zheng X;Pan Y;Zhao L;Kang J;Yang G;Shi Y;Wu K;Gong T;Fan D

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食管鳞状细胞癌(ESCC)患者预后不良的主要原因是淋巴结(LN)转移。 在本研究中,进行了基因表达谱分析(GEP)以确定伴有淋巴结转移(N +)的原发性ESCC肿瘤与无淋巴结转移(N -)的肿瘤之间基因表达谱的差异。 与N -肿瘤相比,在N +的ESCC肿瘤中,共鉴定出23个基因显著上调,30个基因显著下调。在这些基因中,短链脱氢酶/还原酶家族9C成员7(SDR9C7)的两种转录本在N +肿瘤中出现的频率是N -肿瘤的7倍。免疫组化染色显示SDR9C7表达与转移密切相关,并且可能是ESCC患者的一个预后标志物。为了研究SDR9C7在ESCC转移中的作用,采用重复的Transwell实验建立了高侵袭性和非侵袭性ESCC亚系,蛋白质印迹显示高侵袭性细胞中SDR9C7的表达明显高于非侵袭性细胞。SDR9C7的下调在体外和体内显著抑制了转移能力,并抑制了高侵袭性细胞中MMP11的表达,这表明SDR9C7部分通过调节MMP11促进ESCC转移,并且可能是ESCC患者潜在的预后和治疗标志物。
Background The major reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients is lymph node (LN) metastases. Methodology/Principal In the present study, gene expression profiling assay (GEP) was performed to identify the differences in gene expression profiles between primary ESCC tumors that were with LN metastases (N+) and those without LN metastases (N-). Conclusions/Significance A total of 23 genes were identified as being significantly elevated, and 30 genes were sharply decreased in ESCC tumors that were N+ compared with N- tumors. Among these genes, two transcripts of the short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) were observed 7 times more frequently in N+ compared with N- tumors. Immunohistochemical staining showed that SDR9C7 expression closely correlated with metastasis, and would be a prognostic marker for ESCC patients. To investigate the role of SDR9C7 in the ESCC metastasis, repeated transwell assays were adopted to establish highly and non-invasive ESCC sublines, and western blot showed that SDR9C7 expression was markedly higher in highly invasive cells compared with non-invasive ones. Down-regulation of SDR9C7 dramatically inhibited the metastatic abilities in vitro and in vivo, and repressed the expression of MMP11 in highly invasive cells, indicating that SDR9C7 promotes ESCC metastasis partly through regulation of MMP11, and might be a potential prognostic and therapeutic marker for ESCC patients.
MiR-218通过靶向Robo1受体抑制胃癌的侵袭和转移。
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