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Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer
Published on: July 18, 2017
A novel long non-coding RNA-KAT7 is low expressed in colorectal cancer and acts as a tumor suppressor
Qingmei Wang1,2, Rongzhang He1,3, Tan Tan1,2
11Translational Medicine Institute, National & Local Joint Engineering Laboratory for High-throughput Molecular Diagnosis Technology, The First People's Hospital of Chenzhou, University of South China, Chenzhou, 423000 People's Republic of China.
Background:
The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported in the progression of various tumors. However, the potential biological roles and regulatory mechanisms of long non-coding RNAs in the development of colorectal cancer (CRC) have not yet been fully elucidated. Therefore, it is crucial to identify that lncRNAs can be used for the clinical prevention and treatment of CRC.
Methods:
In our previous work, we identificated a novel lncRNA, lncRNA-KAT7, and found that the expression of lncRNA-KAT7 in CRC tissues was significantly lower than that in matched normal intestinal tissues, and the expression in CRC cell lines was lower than that of normal intestinal epithelial cells (P < 0.05). Besides, the expression of lncRNA-KAT7 is negative associated with age, tumor size, tumor differentiation, lymph node metastasis of CRC patients. The potential biological effects and molecular mechanisms of lncRNA-KAT7 in CRC were evaluated using a series of CCK-8 assay, clone formation assay, EdU proliferation assay, scratch determination, transwell determination, western blot analysis, and nude subcutaneous tumorigenesis model construction cell and animal experiments.
Results:
The expression of lncRNA-KAT7 in CRC tissues was lower than that in matched normal tissues and normal intestinal epithelial cells (P < 0.05). Decreased expression of lncRNA-KAT7 is associated with clinicopathological features of poor CRC patients. In vitro experiments showed that up-regulation of lncRNA-KAT7 expression in CRC cells inhibited cell proliferation and migration. In vivo animal experiments showed that the lncRNA-KAT7 also inhibited tumor growth. Western blot analysis showed that the expression of lncRNA-KAT7 was up-regulated in HCT116 cells, the expression of E-cadherin increased, and the expression of Vimentin, MMP-2 and β-catenin protein was down-regulated so did the phosphorylation NF-κB P65. The results confirm that the expression of lncRAN-KAT7 can inhibit the malignant phenotype of CRC cells.
Conclusions:
Up to now, as a novel lncRNA, lncRNA-KAT7 has not any relevant research and reports. The results confirm that the expression of lncRNA-KAT7 can inhibit the malignant phenotype of CRC cells. And it can be used as a new diagnostic biomarker and therapeutic target for the development of CRC.
Insights
This study identifies lncRNA-KAT7 as a novel long non-coding RNA that is downregulated in colorectal cancer (CRC). Its upregulation inhibits CRC cell proliferation, migration, and tumor growth, suggesting its potential as a diagnostic biomarker and therapeutic target for CRC.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Abnormal long non-coding RNA (lncRNA) expression is implicated in various cancers.
- The specific roles of lncRNAs in colorectal cancer (CRC) development remain largely uncharacterized.
- Identifying novel lncRNAs is crucial for CRC's clinical prevention and treatment.
Purpose of the Study:
- To investigate the role and mechanism of the novel lncRNA-KAT7 in colorectal cancer.
- To assess lncRNA-KAT7 as a potential diagnostic biomarker and therapeutic target for CRC.
Main Methods:
- Compared lncRNA-KAT7 expression in CRC tissues/cells versus normal controls.
- Analyzed the association between lncRNA-KAT7 expression and CRC clinicopathological features.
- Evaluated the functional impact of lncRNA-KAT7 on CRC cell proliferation, migration, and invasion in vitro.
- Assessed the effect of lncRNA-KAT7 on tumor growth in vivo using a xenograft model.
- Investigated the molecular mechanisms involving key proteins and signaling pathways via Western blot.
Main Results:
- lncRNA-KAT7 expression was significantly lower in CRC tissues and cells compared to normal controls.
- Decreased lncRNA-KAT7 expression correlated with adverse clinicopathological features in CRC patients.
- Upregulation of lncRNA-KAT7 inhibited CRC cell proliferation, migration, and invasion in vitro.
- lncRNA-KAT7 suppressed tumor growth in vivo.
- lncRNA-KAT7 modulated the expression of E-cadherin, Vimentin, MMP-2, β-catenin, and NF-κB signaling.
Conclusions:
- lncRNA-KAT7 acts as a tumor suppressor in colorectal cancer.
- lncRNA-KAT7 inhibits the malignant phenotype of CRC cells by affecting proliferation, migration, and invasion.
- lncRNA-KAT7 represents a promising novel diagnostic biomarker and therapeutic target for colorectal cancer.
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