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miR-93-5p/IFNAR1 轴通过激活 STAT3 信号通路促进胃癌转移。

miR-93-5p/IFNAR1 axis promotes gastric cancer metastasis through activating the STAT3 signaling pathway.

机构信息

Department of Gastroenterology, No. 254 Hospital of PLA, Tianjin, 300142, PR China.

Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, PR China.

出版信息

Cancer Lett. 2017 Nov 1;408:23-32. doi: 10.1016/j.canlet.2017.08.017. Epub 2017 Aug 24.

Abstract

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.

摘要

miRNAs(微小 RNA)的异常表达在胃癌(GC)的发生发展中起着重要作用。miR-93-5p 在不同类型的癌症中表现出相反的功能,但 miR-93-5p 在 GC 发展中的确切表达模式和分子机制仍有待阐明。在这里,我们报道 miR-93-5p 在 GC 组织中的表达水平高于相邻正常组织,并且其过表达与 GC 患者的远处转移和不良预后相关。miR-93-5p 敲低抑制了 GC 细胞在体外和体内的迁移、侵袭和增殖,而其过表达则显示出相反的结果。通过 mRNA 微阵列,我们发现 miR-93-5p 显著下调了 GC 细胞中 IFNAR1 的表达,IFNAR1 进一步被鉴定为 miR-93-5p 的直接靶标。IFNAR1 敲低促进了 GC 细胞的迁移和侵袭,但它的恢复可以挽救由 miR-93-5p 过表达引起的 GC 细胞迁移和侵袭。此外,miR-93-5p-IFNAR1 轴通过 GC 细胞中的 STAT3 通路增加 MMP9 的表达。综上所述,我们揭示了 miR-93-5p 的过表达与 GC 患者的不良预后相关,miR-93-5p-IFNAR1 轴通过激活 STAT3 通路促进 GC 转移。

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