miR-186 affects the proliferation, invasion and migration of human gastric cancer by inhibition of Twist1.
miR-186 affects the proliferation, invasion and migration of human gastric cancer by inhibition of Twist1.
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DOI：
10.18632/oncotarget.13182
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发表时间：
2016-11-29
期刊：
影响因子：
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通讯作者：
Song L
中科院分区：
文献类型：
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作者：
Cao C;Sun D;Zhang L;Song L
最近的证据表明，miRNA 在包括胃癌 (GC) 在内的多种癌症中失调，并成为关键的癌基因或肿瘤抑制基因。本研究采用qRT-PCR分析miR-186在GC组织及癌旁非癌组织中的表达情况，然后通过更多的体外实验探讨miR-186在GC细胞中的作用。在这里，我们发现 miR-186 在 GC 组织中普遍下调；然而，Twist1 在 GC 组织中普遍上调。此外，miR-186和Twist1与较大的肿瘤大小和GC的晚期临床分期相关。体外实验表明，miR-186的异位过度表达抑制GC细胞增殖、侵袭和迁移；然而，抑制 miR-186 的表达会增强细胞增殖、侵袭和迁移。此外，荧光素酶报告基因测定证明 Twist1 是 miR-186 的直接靶标。最后，Twist1 的过度表达消除了 miR-186 对细胞增殖、侵袭和迁移的抑制作用。总之，miR-186通过抑制Twist1影响人胃癌的增殖、侵袭和迁移，并且可能是GC发展中的肿瘤抑制因子。因此，miR-186可以作为人类胃癌的候选预后生物标志物和新疗法的靶点。
Recent evidence shows that miRNAs are dysregulated in a variety of cancers including gastric cancer (GC), and emerging as key oncogenes or tumor suppressors. In this study, qRT-PCR was used to analyze the expression of miR-186 in GC tissues and adjacent non-cancerous tissues, and then more in-vitro experiments were used to investigate the role of miR-186 in GC cells. Here, we identified miR-186 was generally down-regulated in GC tissues; however, Twist1 was generally up-regulated in GC tissues. Moreover, miR-186 and Twist1 were associated with larger tumor size and advanced clinical stage of GC. In-vitro experiments demonstrated that ectopic overexpression of miR-186 inhibited GC cell proliferation, invasion and migration; however, inhibited expression of miR-186 enhanced cell proliferation, invasion and migration. Furthermore, the luciferase reporter assay demonstrated Twist1 as a direct target of miR-186. Finally, over-expression of Twist1 abrogated inhibitory impact of miR-186 on cell proliferation, invasion and migration. In conclusion, miR-186 affects the proliferation, invasion and migration of human gastric cancer by inhibition of Twist1, and could be a tumor suppressor in GC development. Thus, miR-186 may be served as a candidate prognostic biomarker and target for new therapies in human gastric cancer.