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Updated: May 23, 2026
Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters
Naohiro Nishida1, Makoto Nagahara, Tetsuya Sato
1Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Oita, Japan.
Purpose:
Cancer stroma plays an important role in the progression of cancer. Although alterations in miRNA expression have been explored in various kinds of cancers, the expression of miRNAs in cancer stroma has not been explored in detail.
Experimental Design:
Using a laser microdissection technique, we collected RNA samples specific for epithelium or stroma from 13 colorectal cancer tissues and four normal tissues, and miRNA microarray and gene expression microarray were carried out. The expression status of miRNAs was confirmed by reverse transcriptase PCR. Furthermore, we investigated whether miRNA expression status in stromal tissue could influence the clinicopathologic factors.
Results:
Oncogenic miRNAs, including two miRNA clusters, miR-17-92a and miR-106b-25 cluster, were upregulated in cancer stromal tissues compared with normal stroma. Gene expression profiles from cDNA microarray analyses of the same stromal tissue samples revealed that putative targets of these miRNA clusters, predicted by Target Scan, such as TGFBR2, SMAD2, and BMP family genes, were significantly downregulated in cancer stromal tissue. Downregulated putative targets were also found to be involved in cytokine interaction and cellular adhesion. Importantly, expression of miR-25 and miR-92a in stromal tissues was associated with a variety of clinicopathologic factors.
Conclusions:
Oncogenic miRNAs were highly expressed in cancer stroma. Although further validation is required, the finding that stromal miRNA expression levels were associated with clinicopathologic factors suggests the possibility that miRNAs in cancer stroma are crucially involved in cancer progression.
Insights
Oncogenic microRNAs (miRNAs) are highly expressed in colorectal cancer stroma, potentially driving cancer progression. Stromal miRNA levels correlate with clinicopathologic factors, suggesting a significant role in tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer stroma significantly influences tumor progression.
- MicroRNA (miRNA) expression alterations are implicated in various cancers.
- Detailed investigation of miRNA expression within cancer stroma is lacking.
Purpose of the Study:
- To explore miRNA expression in colorectal cancer stroma.
- To investigate the relationship between stromal miRNA expression and clinicopathologic factors.
Main Methods:
- Laser microdissection to isolate stromal RNA from colorectal cancer and normal tissues.
- miRNA and gene expression microarrays.
- Reverse transcriptase PCR for miRNA validation.
- Correlation analysis between stromal miRNA expression and clinicopathologic factors.
Main Results:
- Oncogenic miRNA clusters (miR-17-92a, miR-106b-25) were upregulated in cancer stroma.
- Putative miRNA targets (e.g., TGFBR2, SMAD2) were downregulated in cancer stroma.
- Stromal miR-25 and miR-92a expression correlated with clinicopathologic factors.
Conclusions:
- Highly expressed oncogenic miRNAs in cancer stroma suggest a role in cancer progression.
- Stromal miRNA expression levels are associated with clinicopathologic factors, warranting further investigation.
