title: Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Oita, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishida
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagahara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sato
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Kohei
authors.initials: K
authors.lastname: Shibata
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D062085:RNA, Long Noncoding; D017154:Stromal Cells / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C568997:MIR17HG, human; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding