miR 1296-5p Inhibits the Migration and Invasion of Gastric Cancer Cells by Repressing ERBB2 Expression.
miR 1296-5p Inhibits the Migration and Invasion of Gastric Cancer Cells by Repressing ERBB2 Expression.
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miR 1296-5p通过抑制ERBB2表达抑制胃癌细胞的迁移和侵袭
DOI：
10.1371/journal.pone.0170298
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Shan X;Wen W;Zhu D;Yan T;Cheng W;Huang Z;Zhang L;Zhang H;Wang T;Zhu W;Zhu Y;Zhu J
胃癌是最常见的肿瘤之一，其转移的分子机制仍不清楚。在这里，我们研究了可能的肿瘤抑制因子miR-1296-5p在erbb2阳性胃癌细胞迁移和侵袭中的作用。发现miR-1296-5p在胃癌组织中显著下调。与非转移性胃癌组织相比，其在淋巴结转移性胃癌组织中表达下调。在SNU-216和NUGC-4胃癌细胞中构建的ERBB2 3'-非翻译区域报告基因的荧光素酶活性表明，ERBB2是miR-1296-5p的靶基因。过表达miR-1296-5p降低其靶蛋白水平和Rac1激活，抑制SNU-216和NUGC-4胃癌细胞的迁移和侵袭。与erbb2阴性胃癌组织相比，erbb2阳性胃癌组织中MiR-1296-5p表达下调。在erbb2阳性胃癌中，与非转移性胃癌样本相比，大多数转移性淋巴结组织中miR-1296-5p的表达被抑制。miR-1296-5p过表达或赫赛汀治疗可抑制胃癌细胞的迁移和侵袭，过表达组成型活性Rac1-Q61L或ERBB2可挽救胃癌细胞。综上所述，我们的研究结果首先表明miR-1296-5p可能至少部分通过靶向ERBB2/Rac1信号通路参与调控人胃癌细胞的迁移和侵袭。
The metastasis of gastric cancer, one of the most common tumors, has a molecular mechanism that is still largely unclear. Here we investigated the role of possible tumor-suppressor miR-1296-5p in the cell migration and invasion of ERBB2-positive gastric cancer. It found that miR-1296-5p was significantly down-regulated in gastric cancer tissues. Moreover, it was down-regulated in lymph node metastatic gastric cancer tissues compared with non-metastatic gastric cancer tissues. The luciferase activity of ERBB2 3'-untranslated region-based reporters constructed in SNU-216 and NUGC-4 gastric cancer cells suggested that ERBB2 was the target gene of miR-1296-5p. Overexpressed miR-1296-5p reduced its target protein level and Rac1 activation, and inhibited the migration and invasion of SNU-216 and NUGC-4 gastric cancer cells. MiR-1296-5p was down-regulated in ERBB2-positive gastric cancer tissues compared with ERBB2-negative gastric cancer tissues. In ERBB2-positive gastric cancers, the miR-1296-5p expression was suppressed in a majority of metastatic lymph node tissues compared to non-metastatic gastric cancer samples. The migration and invasion of gastric cancer cells was inhibited by miR-1296-5p overexpression or herceptin treatment, and rescued by the overexpression of constitutively active Rac1-Q61L or ERBB2. Taken together, our findings first suggest that miR-1296-5p might be involved in the regulation on the migration and invasion of human gastric cancer cells at least in part via targeting ERBB2/Rac1 signaling pathway.