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