ABSTRACT

Gastric cancer is one of the top three leading causes of cancer-related death in the world. Evidence indicated that miR-4677-3p was dysregulated and involved in modulating invasion and migration in multiple types of cancer cells. The aim of this research is to explore the function and mechanism of miR-4677-3p in the development of gastric cancer. In this study, we discovered that miR-4677-3p was down-regulated in gastric cancer tissues and cells. Over-expression of miR-4677-3p suppressed the proliferation, migration and invasion of gastric cancer cells. Furthermore, miR-4677-3p directly bond to CEMIP 3ʹUTR region and inhibited CEMIP expression. CEMIP promoted cell proliferation, migration and invasion of gastric cancer cells via accelerating PI3K/AKT signaling pathway. siCEMIP or PI3K/AKT signaling inhibitor (Akti-1/2 and LY294002) partly reversed the effects of miR-4677-3p on the cellular growth and metastasis of gastric cancer. In general, miR-4677-3p regulated the development of gastric cancer through CEMIP-PI3K/AKT signaling pathway axis. This study verified the function and molecular mechanism of miR-4677-3p in gastric cancer cells, and may provide a potential diagnosis/prognosis target for patients with gastric cancer.

摘要

胃癌是全球三大癌症相关死亡原因之一。有证据表明 miR-4677-3p 失调并参与调节多种癌细胞的侵袭和迁移。本研究旨在探讨miR-4677-3p在胃癌发生发展中的作用及机制。在本研究中，我们发现 miR-4677-3p 在胃癌组织和细胞中下调。miR-4677-3p的过表达抑制了胃癌细胞的增殖、迁移和侵袭。此外，miR-4677-3p 直接与 CEMIP 3ʹUTR 区域结合并抑制 CEMIP 表达。CEIP通过加速PI3K/AKT信号通路促进胃癌细胞增殖、迁移和侵袭。siCEIP 或 PI3K/AKT 信号抑制剂（Akti-1/2 和 LY294002）部分逆转了 miR-4677-3p 对胃癌细胞生长和转移的影响。总体而言，miR-4677-3p 通过 CEMIP-PI3K/AKT 信号通路轴调节胃癌的发展。本研究验证了miR-4677-3p在胃癌细胞中的功能和分子机制，可能为胃癌患者提供潜在的诊断/预后靶点。