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微小RNA-520a-3p的上调通过纺锤体和动粒相关蛋白2抑制胃癌的增殖、迁移和侵袭。

Upregulation of microRNA-520a-3p inhibits the proliferation, migration and invasion via spindle and kinetochore associated 2 in gastric cancer.

作者信息

Su Hui, Ren Feng, Jiang Haitao, Chen Yunjie, Fan Xiaoxiang

机构信息

Department of General Surgery, Ningbo No. 2 Hospital, Zhejiang 315010, P.R. China.

Department of Interventional Therapy, Ningbo No. 2 Hospital, Zhejiang 315010, P.R. China.

出版信息

Oncol Lett. 2019 Sep;18(3):3323-3330. doi: 10.3892/ol.2019.10663. Epub 2019 Jul 25.

Abstract

MicroRNAs (miR) serve important roles in the development and progression of tumors by targeting different genes. miR-520a-3p reported in lung and breast cancers as a tumor suppressor gene. However, the expression and functional significance of miR-520a-3p is not completely understood in gastric cancer (GC). In the present study, it was demonstrated that the expression levels of miR-520a-3p were significantly downregulated in GC tissues and cells using RT-qPCR. In addition, downregulated expression of miR-520a-3p was associated with the clinical stage of the tumor and invasion in patients with GC. Furthermore, overexpression of miR-520a-3p significantly inhibited cell proliferation, invasion and migration in SGC-7901 and MGC-803 GC cell lines using proliferation, wound healing and cell invasion assays. Spindle and kinetochore associated 2 (SKA2) was upregulated in GC cells using western blot analysis and a target gene of miR-520a-3p; miR-520a-3p mimics significantly reduced SKA2 expression. In addition, upregulation of SKA2 protein expression SKA2 reversed the miR-520a-3p-mediated inhibition of SGC-7901 cell proliferation, migration and invasion. In conclusion, miR-520a-3p functioned as a tumor suppressor gene by targeting SKA2 in GC cell lines, and may serve as a novel prognostic and potential therapeutic marker.

摘要

微小RNA(miR)通过靶向不同基因在肿瘤的发生和发展中发挥重要作用。miR-520a-3p在肺癌和乳腺癌中被报道为一种肿瘤抑制基因。然而,miR-520a-3p在胃癌(GC)中的表达及功能意义尚未完全明确。在本研究中,通过逆转录定量聚合酶链反应(RT-qPCR)证明,miR-520a-3p在GC组织和细胞中的表达水平显著下调。此外,miR-520a-3p表达下调与GC患者的肿瘤临床分期及侵袭相关。再者,使用增殖、伤口愈合和细胞侵袭实验,miR-520a-3p过表达显著抑制SGC-7901和MGC-803 GC细胞系的细胞增殖、侵袭和迁移。通过蛋白质印迹分析发现,纺锤体和动粒相关蛋白2(SKA2)在GC细胞中上调,且是miR-520a-3p的靶基因;miR-520a-3p模拟物显著降低SKA2表达。此外,SKA2蛋白表达上调可逆转miR-520a-3p介导的对SGC-7901细胞增殖、迁移和侵袭的抑制作用。总之,在GC细胞系中,miR-520a-3p通过靶向SKA2发挥肿瘤抑制基因的作用,可能作为一种新的预后和潜在治疗标志物。

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