miR-140-5p 通过调节 YES1 抑制胃癌的增殖、迁移和侵袭。

miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1.

机构信息

Department of General Surgery, First affiliated Hospital of Anhui Medical University, 218 Jixi Avenue, Hefei, 230022, China.

Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of University of Munich, Marchioninistr.15, 5H-02-428, 81377, Munich, Germany.

出版信息

Mol Cancer. 2017 Aug 17;16(1):139. doi: 10.1186/s12943-017-0708-6.

BACKGROUND

The aberrant expression of microRNA-140-5p (miR-140-5p) has been described in gastric cancer (GC). However, the role of miR-140-5p in GC remains unclear. In this study, the prognostic relevance of miR-140-5p in GC was investigated and YES1 was identified as a novel target of miR-140-5p in regulating tumor progression.

METHODS

miR-140-5p level was determined in 20 paired frozen specimens through quantitative real-time PCR, and analyzed in tissue microarrays through in situ hybridization. The target of miR-140-5p was verified through a dual luciferase reporter assay, and the effects of miR-140-5p on phenotypic changes in GC cells were investigated in vitro and in vivo.

RESULTS

Compared with that in adjacent normal tissues, miR-140-5p expression decreased in cancerous tissues. The downregulated miR-140-5p in 144 patients with GC was significantly correlated with the reduced overall survival of these patients. miR-140-5p could inhibit GC cell proliferation, migration and invasion by directly targeting 3'-untranlated region of YES1. miR-140-5p could also remarkably reduce the tumor size in GC xenograft mice.

CONCLUSIONS

miR-140-5p serves as a potential prognostic factor in patients with GC, and miR-140-5p mediated YES1 inhibition is a novel mechanism behind the suppressive effects of miR-140-5p in GC.

背景

微小 RNA-140-5p（miR-140-5p）的异常表达已在胃癌（GC）中描述。然而，miR-140-5p 在 GC 中的作用仍不清楚。在这项研究中，研究了 miR-140-5p 在 GC 中的预后相关性，并确定 YES1 是 miR-140-5p 调节肿瘤进展的新靶标。

方法

通过实时定量 PCR 测定 20 对冷冻标本中的 miR-140-5p 水平，并通过原位杂交在组织微阵列中进行分析。通过双荧光素酶报告基因实验验证 miR-140-5p 的靶标，并在体外和体内研究 miR-140-5p 对 GC 细胞表型变化的影响。

结果

与相邻正常组织相比，癌症组织中 miR-140-5p 的表达降低。在 144 例 GC 患者中下调的 miR-140-5p 与这些患者总生存时间的降低显著相关。miR-140-5p 可以通过直接靶向 YES1 的 3'非翻译区来抑制 GC 细胞的增殖、迁移和侵袭。miR-140-5p 还可以显著减少 GC 异种移植小鼠的肿瘤体积。