MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival
MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival
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MicroRNA-25 通过直接靶向 ERBB2, 1 转导子促进胃癌迁移、侵袭和增殖，并与较差的生存率相关
DOI：
10.1038/onc.2014.214
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发表时间：
2015-05-14
期刊：
影响因子：
8
通讯作者：
Guo, G.
中科院分区：
文献类型：
--
作者：
Li, B-S;Zuo, Q-F;Guo, G.
胃癌是最常见的恶性肿瘤之一，其转移的分子机制尚不清楚。在这里，我们发现miR-25在肿瘤淋巴结转移期（III或IV）或淋巴结转移的GC患者的血浆和原发肿瘤组织中过表达。miR-25抑制显著降低了体外GC细胞的转移、侵袭和增殖，并降低了其体内发展远端肺转移和腹膜播散的能力。此外，miR-25通过与TOB 1 - 3 '-UTR直接结合抑制ERBB 2，1（TOB 1）的表达，并且在原代胃癌组织中miR-25与TOB 1 mRNA的表达呈负相关。TOB 1基因缺失可促进胃癌细胞的转移、侵袭和增殖，而TOB 1基因恢复则可抑制胃癌细胞的转移、侵袭和增殖。受试者工作特征分析得出的曲线下面积值为0.7325，用于区分死亡的GC患者和存活的GC患者。对最佳截止值的分析显示，具有高血浆miR-25浓度（40.2333阿莫尔/μ l）的GC患者的生存率较差。综上所述，miR-25通过直接下调TOB 1表达促进GC进展，并且可能是GC患者预后的非侵入性生物标志物。
Gastric cancer (GC) is one of the most common tumors and the molecular mechanism underlying its metastasis is still largely unclear. Here, we show that miR-25 was overexpressed in plasma and primary tumor tissues of GC patients with tumor node metastasis stage (III or IV) or lymph node metastasis. MiR-25 inhibition significantly decreased the metastasis, invasion and proliferation of GC cells in vitro, and reduced their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Furthermore, miR-25 repressed transducer of ERBB2, 1 (TOB1) expression by directly binding to TOB1-3'-UTR, and the inverse correlation was observed between the expressions of miR-25 and TOB1 mRNA in primary GC tissues. Moreover, the loss of TOB1 increased the metastasis, invasion and proliferation of GC cells, and the restoration of TOB1 led to suppressed metastasis, invasion and proliferation. The receiver operating characteristics analysis yielded an area under the curve value of 0.7325 in distinguishing the GC patients with death from those with survival. The analysis of optimal cutoff value revealed poor survival in GC patients with high plasma concentrations of miR-25 (40.2333 amol/mu l). Taken together, miR-25 promotes GC progression by directly downregulating TOB1 expression, and may be a noninvasive biomarker for the prognosis of GC patients.