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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
A New Light on Potential Therapeutic Targets for Colorectal Cancer Treatment
Wei-Lun Tsai1, Chih-Yang Wang2,3, Yu-Cheng Lee4
1PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.
Abstract:
The development and progression of colorectal cancer (CRC) involve changes in genetic and epigenetic levels of oncogenes and/or tumor suppressors. In spite of advances in understanding of the molecular mechanisms involved in CRC, the overall survival rate of CRC still remains relatively low. Thus, more research is needed to discover and investigate effective biomarkers and targets for diagnosing and treating CRC. The roles of long non-coding RNAs (lncRNAs) participating in various aspects of cell biology have been investigated and potentially contribute to tumor development. Our recent study also showed that CRNDE was among the top 20 upregulated genes in CRC clinical tissues compared to normal colorectal tissues by analyzing a Gene Expression Omnibus (GEO) dataset (GSE21815). Although CRNDE is widely reported to be associated with different types of cancer, most studies of CRNDE were limited to examining regulation of its transcription levels, and in-depth mechanistic research is lacking. In the present study, CRNDE was found to be significantly upregulated in CRC patients at an advanced TNM stage, and its high expression was correlated with poor outcomes of CRC patients. In addition, we found that knocking down CRNDE could reduce lipid accumulation through the miR-29b-3p/ANGPTL4 axis and consequently induce autophagy of CRC cells.
Insights
Colorectal cancer (CRC) progression is linked to the long non-coding RNA CRNDE. Reducing CRNDE lowers lipid accumulation and induces cell death, offering potential new CRC treatments.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) remains a significant health concern with low survival rates despite advances in understanding its molecular basis.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in various cellular processes, including cancer development.
- The lncRNA CRNDE has been identified as upregulated in CRC, but its specific functions and mechanisms require further investigation.
Purpose of the Study:
- To investigate the functional role and underlying mechanisms of CRNDE in colorectal cancer progression.
- To determine the correlation between CRNDE expression levels and clinical outcomes in CRC patients.
- To explore CRNDE's potential as a therapeutic target for CRC.
Main Methods:
- Analysis of a Gene Expression Omnibus (GEO) dataset (GSE21815) to identify upregulated genes in CRC.
- Quantitative analysis of CRNDE expression in CRC tissues and correlation with TNM stage and patient outcomes.
- Experimental manipulation of CRNDE levels (e.g., knockdown) in CRC cells.
- Investigation of the molecular pathways involved, including the miR-29b-3p/ANGPTL4 axis and autophagy.
Main Results:
- CRNDE was significantly upregulated in CRC tissues and correlated with advanced TNM stage and poor patient survival.
- Knocking down CRNDE expression led to reduced lipid accumulation in CRC cells.
- The observed effects were mediated through the miR-29b-3p/ANGPTL4 axis, subsequently inducing autophagy in CRC cells.
Conclusions:
- CRNDE is a key oncogenic lncRNA in colorectal cancer, associated with advanced disease and poor prognosis.
- Targeting CRNDE may offer a novel therapeutic strategy for CRC by modulating lipid metabolism and inducing autophagy.
- The miR-29b-3p/ANGPTL4 axis represents a critical pathway through which CRNDE influences CRC cell behavior.
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