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Updated: Nov 8, 2025
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
let-7e downregulation characterizes early phase colonic adenoma in APCMin/+ mice and human FAP subjects
Annalisa Contursi1,2, Maria Arconzo1,3, Marica Cariello1,3
1Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", Bari, Italy.
Abstract:
The crypt-villus axis represents the essential unit of the small intestine, which integrity and functions are fundamental to assure tissue and whole-body homeostasis. Disruption of pathways regulating the fine balance between proliferation and differentiation results in diseases development. Nowadays, it is well established that microRNAs (miRNAs) play a crucial role in the homeostasis maintenance and perturbation of their levels may promote tumor development. Here, by using microarray technology, we analysed the miRNAs differentially expressed between the crypt and the villus in mice ileum. The emerged miRNAs were further validated by Real Time qPCR in mouse model (ApcMin/+), human cell lines and human tissue samples (FAP) of colorectal cancer (CRC). Our results indicated that miRNAs more expressed in the villi compartment are negatively regulated in tumor specimens, thus suggesting a close association between these microRNAs and the differentiation process. Particularly, from our analysis let-7e appeared to be a promising target for possible future therapies and a valuable marker for tumor staging, being upregulated in differentiated cells and downregulated in early-stage colonic adenoma samples.
Insights
MicroRNAs (miRNAs) are crucial for intestinal homeostasis. This study identified specific miRNAs, like let-7e, that are downregulated in colorectal cancer, suggesting their potential as therapeutic targets and staging markers.
Area of Science:
- Gastroenterology
- Molecular Biology
- Oncology
Background:
- The crypt-villus axis is vital for small intestine integrity and homeostasis.
- Dysregulation of proliferation and differentiation pathways contributes to disease development.
- MicroRNAs (miRNAs) are key regulators of homeostasis; their aberrant expression can promote tumor development.
Purpose of the Study:
- To analyze differentially expressed miRNAs between mouse ileum crypt and villus compartments.
- To validate the role of identified miRNAs in colorectal cancer (CRC) progression.
- To identify potential miRNA biomarkers for CRC diagnosis and therapy.
Main Methods:
- Microarray analysis of miRNA expression in mouse ileum crypt and villus.
- Quantitative real-time PCR (qPCR) validation in mouse models (ApcMin/+) and human CRC samples (FAP).
- Analysis of miRNA expression in human cell lines and tissue samples.
Main Results:
- Identified miRNAs differentially expressed between crypt and villus compartments in mouse ileum.
- Demonstrated that villus-enriched miRNAs are downregulated in colorectal cancer specimens.
- Highlighted let-7e as upregulated in differentiated cells and downregulated in early-stage colonic adenomas.
Conclusions:
- Specific miRNAs are closely associated with the intestinal differentiation process.
- let-7e shows promise as a therapeutic target and a staging marker for colorectal cancer.
- Understanding miRNA regulation in the crypt-villus axis is crucial for developing novel cancer therapies.
