Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters

Naohiro Nishida, Makoto Nagahara, Tetsuya Sato, Koshi Mimori, Tomoya Sudo, Fumiaki Tanaka, Kohei Shibata, Hideshi Ishii, Kenichi Sugihara, Yuichiro Doki, Masaki Mori

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3054-3070
Number of pages17
JournalClinical Cancer Research
Volume18
Issue number11
DOIs
Publication statusPublished - Jun 1 2012

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Microarray Analysis
MicroRNAs
Colorectal Neoplasms
Up-Regulation
Neoplasms
Down-Regulation
Microdissection
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Transcriptome
Lasers
Research Design
Epithelium
RNA
Cytokines
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters. / Nishida, Naohiro; Nagahara, Makoto; Sato, Tetsuya; Mimori, Koshi; Sudo, Tomoya; Tanaka, Fumiaki; Shibata, Kohei; Ishii, Hideshi; Sugihara, Kenichi; Doki, Yuichiro; Mori, Masaki.

In: Clinical Cancer Research, Vol. 18, No. 11, 01.06.2012, p. 3054-3070.

Research output: Contribution to journalArticle

Nishida, N, Nagahara, M, Sato, T, Mimori, K, Sudo, T, Tanaka, F, Shibata, K, Ishii, H, Sugihara, K, Doki, Y & Mori, M 2012, 'Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters', Clinical Cancer Research, vol. 18, no. 11, pp. 3054-3070. https://doi.org/10.1158/1078-0432.CCR-11-1078
Nishida, Naohiro ; Nagahara, Makoto ; Sato, Tetsuya ; Mimori, Koshi ; Sudo, Tomoya ; Tanaka, Fumiaki ; Shibata, Kohei ; Ishii, Hideshi ; Sugihara, Kenichi ; Doki, Yuichiro ; Mori, Masaki. / Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 11. pp. 3054-3070.
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