Department of Gastrointestinal Tumor Surgery, The Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, Hunan 410013, P.R. China.
Int J Mol Med. 2014 Nov;34(5):1286-92. doi: 10.3892/ijmm.2014.1909. Epub 2014 Aug 19.
Angiopoietin-like protein 2 (ANGPTL2) is associated with tumor progression while dysregulation of its expression has been observed in various types of cancer. However, the expression and role of ANGPTL2 remain exclusive in colorectal cancer (CRC). In the present study, we determined the expression levels of ANGPTL2 in CRC tissues and cells. The roles of ANGPTL2 and miR-25 in the migration and invasion of CRC SW620 and HCT-116 cells were also investigated using transwell assays or scratch wound assays. The results showed that ANGPTL2 increased with metastatic progression. Increased ANGPTL2 and decreased microRNA-25 (miR-25) expression were found to coexist in CRC. The functional studies revealed that knockdown of ANGPTL2 reduced colony formation, and the invasive and migratory abilities of human CRC SW620 and HCT-116 cells. Similarly, overexpression of miR-25 resulted in reduced colony formation, invasion and migration in both cell lines. The overexpression of miR-25 led to a decreased ANGPTL2 mRNA and protein expression, whereas the downregulation of miR-25 resulted in increased ANGPTL2 mRNA and protein expression, in SW620 and HCT-116 cells. miR-25 directly targeted ANGPTL2 by binding to its 3'‑UTR, as determined by the dual luciferase reporter assay. To the best of our know-ledge, the results of this study suggest for the first time that the abnormal upregulation of ANGPTL2 in CRC is associated with miR-25 downregulation. Additionally, miR-25‑mediated ANGPTL2 promoted the malignant progression of CRC. The present study provides evidence supporting ANGPTL2 and miR-25 as diagnostic or therapeutic targets for CRC.
血管生成素样蛋白 2(ANGPTL2)与肿瘤进展相关,其表达失调已在多种类型的癌症中观察到。然而,ANGPTL2 在结直肠癌(CRC)中的表达和作用仍然是独特的。在本研究中,我们测定了 CRC 组织和细胞中 ANGPTL2 的表达水平。还通过 Transwell 测定或划痕伤口测定研究了 ANGPTL2 和 miR-25 在 CRC SW620 和 HCT-116 细胞迁移和侵袭中的作用。结果表明,ANGPTL2 随转移进展而增加。发现 CRC 中存在 ANGPLT2 增加和 microRNA-25(miR-25)表达降低的现象。功能研究表明,ANGPTL2 敲低可减少人 CRC SW620 和 HCT-116 细胞的集落形成以及侵袭和迁移能力。同样,miR-25 的过表达导致两种细胞系中的集落形成、侵袭和迁移减少。miR-25 的过表达导致 ANGPTL2 mRNA 和蛋白表达降低,而 miR-25 的下调导致 ANGPTL2 mRNA 和蛋白表达增加,在 SW620 和 HCT-116 细胞中。miR-25 通过结合其 3'UTR 直接靶向 ANGPTL2,通过双荧光素酶报告基因测定确定。据我们所知,这项研究的结果首次表明 CRC 中 ANGPTL2 的异常上调与 miR-25 下调有关。此外,miR-25 介导的 ANGPTL2 促进了 CRC 的恶性进展。本研究为 ANGPTL2 和 miR-25 作为 CRC 的诊断或治疗靶点提供了证据。