Angiopoietin-like protein 2 negatively regulated by microRNA-25 contributes to the malignant progression of colorectal cancer

• Published in: International journal of molecular medicine Vol. 34; no. 5; pp. 1286 - 1292
• Main Authors: ZHOU, JUMEI, WANG, JING, WU, SHENGQI, ZHU, SUYU, WANG, SAI, ZHOU, HUIJUN, TIAN, XIAOQING, TANG, NING, NIE, SHAOLIN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.11.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Angiogenesis; angiopoietin-like protein 2; Angiopoietin-like Proteins; Angiopoietins - genetics; Angiopoietins - metabolism; Apoptosis; Cell cycle; Cell Line, Tumor; Cell Movement; Colorectal cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Development and progression; Disease Progression; Down-Regulation; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genes; Growth factors; HCT116 Cells; Humans; Metastasis; MicroRNA; microRNA-25; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Physiological aspects; Proteins; Regulation; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcription factors; Up-Regulation; China; United States > US
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2014.1909

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 knowledge, 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.