Clinical and experimental role of ring finger protein 180 on lymph node metastasis and survival in gastric cancer
Clinical and experimental role of ring finger protein 180 on lymph node metastasis and survival in gastric cancer
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DOI：
10.1002/bjs.10066
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发表时间：
2016-03-01
影响因子：
9.6
通讯作者：
Hao, X.
中科院分区：
文献类型：
--
作者：
Deng, J.;Liang, H.;Hao, X.
背景资料：环指蛋白（RNF）180基因启动子甲基化与胃癌淋巴结转移密切相关。本研究探讨RNF 180调控胃癌淋巴结转移的可能机制。方法：分析RNF 180在胃癌组织中的表达与临床病理及生存资料的关系。通过细胞增殖、侵袭、生长和淋巴管生成实验，观察RNF 180再表达对胃癌细胞的影响。结果：134例胃癌组织中有99例（73.9%）RNF 180表达沉默或下调，而配对的非肿瘤组织中RNF 180表达沉默或下调的比例为41.8%。作为胃癌独立的预后指标，胃癌组织中RNF 180的表达与转移淋巴结数量呈负相关。RNF 180在所有7个胃癌细胞系中也下调。RNF 180在胃癌细胞中的重新表达抑制体外集落形成、增殖、迁移和侵袭; RNF 180的重新表达还抑制小鼠肿瘤生长和淋巴管生成。RNF 180的再表达下调了胃癌细胞中肝细胞生长因子、基质金属蛋白酶2、MMP-14、血管内皮生长因子C/D和趋化因子受体7的表达，下调了裸鼠肿瘤组织中podoplanin的表达。
Background: The hypermethylation of ring finger protein (RNF) 180 DNA promoter is significantly associated with lymph node metastasis of gastric cancer. The present study explored the potential mechanism of RNF180-regulated lymph node metastasis of gastric cancer.Methods: Associations between clinicopathological and survival data and RNF180 expression in gastric cancer tissues were analysed. The effects of RNF180 re-expression on gastric cancer cells were determined by means of proliferation, invasion, growth and lymphangiogenesis assays. A genome microarray was used to find potential target genes associated with lymphatic metastasis of gastric cancer cells regulated by RNF180.Results: RNF180 was silenced or downregulated in 99 (73.9 per cent) of 134 gastric cancer tissues compared with 41.8 per cent of paired non-tumour tissues from patients. As an independent prognostic indicator of gastric cancer, RNF180 expression in gastric cancer tissues was negatively related to the number of metastatic lymph nodes. RNF180 was also downregulated in all seven gastric cancer cell lines examined. The re-expression of RNF180 in gastric cancer cells inhibited colony formation, proliferation, migration and invasion in vitro; re-expression of RNF180 also suppressed tumour growth and lymphangiogenesis in mice. Furthermore, re-expression of RNF180 downregulated the expression of hepatocyte growth factor, matrix metalloproteinase (MMP) 2, MMP-14, vascular endothelial growth factor C/D and chemokine receptor 7 in gastric cancer cells; it also downregulated the expression of podoplanin in tumour tissue of nude mice.Conclusion: RNF180 appears to act as a suppressor gene that inhibits lymph node metastasis in gastric cancer.