National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
General Surgery and Center of Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
Oncogene. 2015 May 14;34(20):2556-65. doi: 10.1038/onc.2014.214. Epub 2014 Jul 21.
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 (>0.2333 amol/μl). Taken together, miR-25 promotes GC progression by directly downregulating TOB1 expression, and may be a noninvasive biomarker for the prognosis of GC patients.
胃癌（GC）是最常见的肿瘤之一，但其转移的分子机制仍很大程度上不清楚。在这里，我们发现 miR-25 在具有肿瘤淋巴结转移分期（III 或 IV 期）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 GC 细胞在体外的转移、侵袭和增殖能力，并降低了它们在体内形成远端肺转移和腹膜扩散的能力。此外，miR-25 通过直接结合 TOB1-3'-UTR 来抑制 ERBB2 转导物 1（TOB1）的表达，并且在原发性 GC 组织中观察到 miR-25 和 TOB1 mRNA 的表达呈负相关。此外，TOB1 的缺失增加了 GC 细胞的转移、侵袭和增殖，而 TOB1 的恢复导致转移、侵袭和增殖受到抑制。受试者工作特征分析在区分死亡和存活的 GC 患者时得出曲线下面积值为 0.7325。对最佳截断值的分析显示，血浆中 miR-25 浓度较高（>0.2333 amol/μl）的 GC 患者生存不良。总之，miR-25 通过直接下调 TOB1 的表达促进 GC 的进展，并且可能是 GC 患者预后的非侵入性生物标志物。
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