miR-93-5p/IFNAR1 axis promotes gastric cancer metastasis through activating the STAT3 signaling pathway
miR-93-5p/IFNAR1 axis promotes gastric cancer metastasis through activating the STAT3 signaling pathway
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DOI：
10.1016/j.canlet.2017.08.017
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发表时间：
2017-11-01
期刊：
影响因子：
9.7
通讯作者：
Yang, Shi-Ming
中科院分区：
文献类型：
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作者：
Ma, Dong-Hong;Li, Bo-Sheng;Yang, Shi-Ming
microRNAs（miRNAs）的异常表达在胃癌的发生发展中起着重要作用。miR-93- 5 p在不同类型的癌症中显示出相反的功能，但miR-93- 5 p在GC发展中的确切表达模式和分子机制仍有待阐明。在此，我们报道了miR-93- 5 p在胃癌组织中的表达高于癌旁正常组织，并且其过表达与胃癌患者的远处转移和不良生存相关。miR-93- 5 p在体内外均能抑制胃癌细胞的迁移、侵袭和增殖，而miR-93- 5 p过表达则相反。使用mRNA微阵列，我们发现miR-93- 5 p显著下调GC细胞中IFNAR 1的表达，其被进一步鉴定为miR-93- 5 p的直接靶点。IFNAR 1基因敲低可促进胃癌细胞的迁移和侵袭，但其恢复可挽救miR-93- 5 p过表达诱导的胃癌细胞迁移和侵袭。此外，miR-93- 5 p-IFNAR 1轴通过STAT 3途径增加GC细胞中MMP 9的表达。综上所述，我们揭示了miR-93- 5 p过表达与胃癌患者的生存率低相关，miR-93- 5 p-IFNAR 1轴通过激活STAT 3通路促进胃癌转移。(C)2017爱思唯尔B. V.保留所有权利。
Aberrant expression of microRNAs (miRNAs) plays an important role in gastric cancer (GC) development. miR-93-5p has shown opposing functions in different types of cancers, but the exact expression pattern and molecular mechanism of miR-93-5p in GC development remain to be elucidated. Here, we reported that miR-93-5p expression was increased in GC tissues compared with the adjacent normal tissues and that its overexpression was correlated with distant metastasis and poor survival in GC patients. miR-93-5p knockdown inhibited the migration, invasion and proliferation of GC cells in vitro and in vivo, while its overexpression displayed an opposite result. Using an mRNA microarray, we found that miR-93-5p significantly downregulated IFNAR1 expression in GC cells, which was further identified as a direct target of miR-93-5p. IFNAR1 knockdown promoted GC cell migration and invasion, but its restoration could rescue GC cell migration and invasion induced by miR-93-5p overexpression. Moreover, miR-93-5p-IFNAR1 axis increased MMP9 expression via STAT3 pathway in GC cells. Taken together, we reveal that miR-93-5p overexpression is associated with the poor survival of GC patients and miR-93-5p-IFNAR1 axis promotes GC metastasis through activation of STAT3 pathway. (C) 2017 Elsevier B.V. All rights reserved.