Abstract

BackgroundAngiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate. Nevertheless, its effects on colorectal cancer (CRC) remain poorly defined. In this study, we aim to demonstrate the biological function of ANGPTL1 in CRC cells.MethodsWe explored ANGPTL1 mRNA expression in human CRC tissues and its association with prognosis. CRC cell lines overexpressing ANGPTL1 or with ANGPTL1 knocked down were constructed and analyzed for changes in proliferation, colony formation, migration and invasion. ANGPTL1-regulated microRNAs were analyzed, and microRNA inhibitor and mimics were used to explore the role of microRNA in ANGPTL1-associated biological function.ResultsANGPTL1 mRNA expression was down-regulated in CRC tissues, and high ANGPTL1 expression predicted better survival in CRC patients. ANGPTL1 overexpression resulted in suppressed migration and invasion in vitro, and it prolonged overall survival in mouse models. By contrast, its down-regulation enhanced migration and invasion of CRC cells. MicroRNA-138 expression was positively correlated with ANGPTL1 mRNA level in CRC tissues and up-regulated by ANGPTL1 in CRC cells. In addition, the microRNA-138 inhibitor or mimics could reverse or promote the ANGPTL1-mediated inhibition of the migratory capacity of CRC cells, respectively.ConclusionsThis study is the first to demonstrate the biological function of ANGPTL1 in CRC cells. ANGPTL1 expression was down-regulated in CRC tissues and inversely correlated with poor survival. ANGPTL1 repressed migration and invasion of CRC cells, and microRNA-138 was involved in this process.

Highlights

  • Angiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate

  • ANGPTL1 has been reported to inhibit the proliferation, migration, tube formation and adhesion of endothelial cells by blocking the MAPK and PI3K/Akt signaling pathways [8, 9]. These findings suggest that ANGPTL1 may act as a novel tumor suppressor candidate in lung and breast cancer

  • ANGPTL1 mRNA expression was down-regulated in colorectal cancer (CRC), and high ANGPTL1 expression correlated with better survival To identify genes of tumorigenic potential, we analyzed gene expression profiles of paired cancerous and normal tissues from The Cancer Genome Atlas (TCGA) datasets

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Summary

Introduction

Angiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate. Its effects on colorectal cancer (CRC) remain poorly defined. As the fourth most common cause of cancer-related deaths globally [1], colorectal cancer (CRC) is a major public health burden in most industrialized countries [2]. The poor efficiency and lack of options for treating metastasis is the major cause of death due to CRC. In our previous study [4], we analyzed the gene expression profiles of paired tumor and normal tissue samples from The Cancer Genome Atlas (TCGA) datasets, and identified a number of genes that are significantly up-regulated or down-regulated in different types of cancer compared to their normal counterparts. We focused on Angiopoietin-like protein 1 (ANGPTL1), which was down-regulated in 87.5% (14/16) of included cancer types. ANGPTLs are a family of proteins that are structurally similar to angiopoietins, comprising ANGPTL1 to ANGPTL7

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