Abstract
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. 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. 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. 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.
Highlights
Cancer tissues consist of cancer cells and surrounding stromal cells, including inflammatory cells, immunocompetent cells, endothelial cells, and fibroblasts
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
We found that oncogenic miRNAs, including the miR-17-92a cluster and the miR-106b-25 cluster, which are known to be involved in cancer progression in epithelial tissue, were significantly upregulated in cancer stromal tissue compared with normal stroma
Summary
Cancer tissues consist of cancer cells and surrounding stromal cells, including inflammatory cells, immunocompetent cells, endothelial cells, and fibroblasts. Finak and colleagues analyzed global gene expression patterns in breast cancer stromal tissues and identified gene sets that potently influenced prognosis [6]. They revealed that the aggressiveness of cancer could be defined by gene expression patterns in stromal tissue. Fukino and colleagues revealed that cancer-specific LOH or allelic imbalance in stromal cells is more highly correlated with clinicopathologic features than that in epithelial cells [7]. These findings suggest that cancer stromal tissues are actively involved in cancer progression
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