ANGPTL1 attenuates colorectal cancer metastasis by up-regulating microRNA-138

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0548-7) contains supplementary material, which is available to authorized users.

Deciphering molecular properties of hypermutated gastrointestinal cancer

“…Co‐expression network analysis revealed that ANK2 was a hub gene associated with some validated tumor suppressors (Figure C). For example, ANGPTL1 and SPARCL1, crosstalking with ANK2, have been shown to attenuate colorectal cancer metastasis in our previous work . Hypermutated patients with higher ANK2 expression levels had a significantly better clinical outcome ( P = 0.00771, log‐rank test, Figure D).…”

Exosomal ANGPTL1 Attenuates CRC Liver Metastasis by Regulating Kupffer Cell Secretion Pattern and Impeding MMP9 induced vascular leakiness.

“…In our previous study [5], we found some of the angiopoietin-like proteins (ANGPTLs) were downregulated in CRC tissue, among which ANGPTL1 was the most signi cant one. ANGPTLs are a family of proteins that are similar to angiopoietins in structure, including ANGPTL1 to ANGPTL8 [6].…”

“…Our previous study also demonstrated that ANGPTL1 overexpression inhibited the migration and invasion of CRC cells, leading liver metastasis suppression. Besides, low expression of ANGPTL1 was related to poorer prognosis in CRC patients [5].…”

“…Early studies showed that Angiopoietin-like protein 1 (ANGPTL1) acts as an anti-angiogenic factor and a tumor suppressor [12,13]. ANGPTL1 is downregulated in various cancers [5,6], and several studies have proved its inhibitory role in tumor growth and metastasis [14][15][16][17].…”

Molecular Dynamics of A Biglycan-Rosmarinic Acid Complex with Focal Adhesion Kinase for Possible Arrest of Metastasis in Non-Small Cell Lung Cancer (NSCLC): An In- Silico Study

“…However, significant progress is ongoing in both the prevention and treatment of lung cancer 4 . Many integrated multidisciplinary approaches to the treatment of lung cancer have improved patient outcomes, but there is an urgent need for a novel therapeutic strategy for lung cancer as there is no breakthrough treatment with long-term efficacy 5 . Specifically improved proteomics techniques for the identification, detection, and verification of biomarkers have improved our understanding of lung cancer but, early detection of lung cancer is important for a better outcome and to decrease the lung cancer mortality rate 6,7 .…”