ABSTRACT

Colon cancer is the third most common cancer worldwide. Many miRNAs have been reported to be involved in colon cancer progression. However, there are only a few studies on the role of miR-219a-1 in colon cancer, and the molecular mechanisms involved remain unclear. The aim of this study was to investigate the miR-219a-1 level in patients with colon cancer and to explore both the effects and regulatory mechanisms of miR-219a-1 in the malignancy of colon cancer cells. Real-time PCR and western blot analysis were used to analyze the expression levels of miR-219a-1 and mediator of ErbB2-driven cell motility 1. Cell Counting Kit-8, transwell and wound-healing assays were performed to investigate the malignant ability of colon cancer cells. A luciferase assay was performed to explore whether miR-219a-1 could directly bind to 3ʹ-UTR region of MEMO1. miR-219a-1 was found to be downregulated in colon cancer cell lines and in patients with colon cancer. Additionally, miR-219a-1 could inhibit colon cancer cell proliferation, invasion and migration. We identified MEMO1 as a novel potential target gene of miR-219a-1. Luciferase assays showed that miR-219a-1 could directly bind to 3′-UTR of MEMO1. Overexpression of miR-219a-1 in colon cancer cells could inhibit the expression of MEMO1. Furthermore, MEMO1 was upregulated in patients with colon cancer, which was inversely correlated with miR-219a-1 levels. In conclusion, our study revealed that miR-219a-1 exerts anti-tumor effects and regulates colon cancer cell proliferation, invasion and migration by targeting MEMO1, suggesting that miR-219a-1 could act as a therapeutic target in colon cancer.

摘要

结肠癌是全球第三大常见癌症。据报道，许多 miRNA 与结肠癌进展有关。然而，关于miR-219a-1在结肠癌中的作用的研究较少，涉及的分子机制尚不清楚。本研究的目的是调查结肠癌患者的 miR-219a-1 水平，并探讨 miR-219a-1 在结肠癌细胞恶性肿瘤中的作用和调控机制。实时荧光定量 PCR 和蛋白质印迹分析用于分析 miR-219a-1 和 ErbB2 驱动的细胞运动介质的表达水平 1. 进行细胞计数试剂盒 8、transwell 和伤口愈合试验以研究恶性能力结肠癌细胞。进行了荧光素酶测定以探索 miR-219a-1 是否可以直接结合到 3ʹ-UTR 区域备忘1。发现 miR-219a-1 在结肠癌细胞系和结肠癌患者中下调。此外，miR-219a-1 可以抑制结肠癌细胞增殖、侵袭和迁移。我们将MEMO1鉴定为 miR-219a-1 的新型潜在靶基因。荧光素酶分析表明，miR-219a-1 可以直接结合MEMO1 的3'-UTR 。miR-219a-1在结肠癌细胞中的过表达可抑制MEMO1的表达。此外，MEMO1在结肠癌患者中上调，这与 miR-219a-1 水平呈负相关。总之，我们的研究表明 miR-219a-1 发挥抗肿瘤作用并通过靶向调节结肠癌细胞的增殖、侵袭和迁移。MEMO1，表明 miR-219a-1 可以作为结肠癌的治疗靶点。