title: MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer.
abstract: Gastric cancer (GC) is one of the most common malignancies worldwide. In particular, scirrhous type GC is highly metastatic and is characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs) play crucial roles in cancer development and progression. In the present study, we identified several miRNAs that are expressed at higher levels in scirrhous type GC than in non-scirrhous type GC by miRNA microarray analysis. Among these, microRNA-143 (miR-143) expression was higher in scirrhous type GC than in non-scirrhous types of GC. In situ hybridization and quantitative RT-PCR analysis showed that miR-143 is expressed by stromal fibroblasts but not by cancer cells. In stromal cells, miR-143 enhanced collagen type III expression in normal gastric fibroblasts and cancer-associated fibroblasts through activation of transforming growth factor-β)/SMAD signaling. Furthermore, high miR-143 expression in GC was associated with worse cancer-specific mortality (P = 0.0141). Multivariate analysis revealed that miR-143 was an independent prognostic factor. Treatment of GC cell lines with 5-aza-2'-deoxycytidine restored the expression of miR-143, and precursor miR-143 caused the inhibition of cancer cell invasion. These data suggest that miR-143 regulates fibrosis of scirrhous type GC through induction of collagen expression in stromal fibroblasts and that miR-143 expression serves as a prognostic marker of GC.
authors.affiliation: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Naito
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D045744:Cell Line, Tumor; D024061:Collagen Type III / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D024061:Collagen Type III; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta
keywords: Collagen type III; fibroblast; gastric cancer; microRNA-143; transforming growth factor-β