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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
ANGPTL1 attenuates colorectal cancer metastasis by up-regulating microRNA-138
Haiyan Chen1,2, Qian Xiao1,2, Yeting Hu1,2
1Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
Background:
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. 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.
Methods:
We 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.
Results:
ANGPTL1 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.
Conclusions:
This 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.
Insights
Angiopoietin-like protein 1 (ANGPTL1) acts as a tumor suppressor in colorectal cancer (CRC). Lower ANGPTL1 levels correlate with poor survival, while its restoration inhibits CRC cell migration and invasion via microRNA-138.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Angiopoietin-like protein 1 (ANGPTL1) is a known tumor suppressor in lung and breast cancers.
- Its specific role in colorectal cancer (CRC) remains largely undefined.
Purpose of the Study:
- To elucidate the biological function of ANGPTL1 in colorectal cancer cells.
- To investigate the prognostic significance of ANGPTL1 in CRC patients.
Main Methods:
- Analysis of ANGPTL1 mRNA expression in human CRC tissues and correlation with patient prognosis.
- Functional assays (proliferation, colony formation, migration, invasion) in CRC cell lines with altered ANGPTL1 levels.
- Investigation of ANGPTL1-regulated microRNAs, including microRNA-138, using inhibitors and mimics.
Main Results:
- ANGPTL1 mRNA expression was significantly down-regulated in CRC tissues.
- High ANGPTL1 expression correlated with improved survival in CRC patients.
- ANGPTL1 overexpression suppressed CRC cell migration and invasion, while knockdown enhanced these processes. MicroRNA-138 was identified as a key mediator.
Conclusions:
- ANGPTL1 functions as a tumor suppressor in colorectal cancer.
- Down-regulation of ANGPTL1 is associated with poor prognosis in CRC.
- ANGPTL1 inhibits CRC cell migration and invasion, partly through its regulation of microRNA-138.
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