MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer.
Bottom Line: 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).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.
Affiliation: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.Show MeSH
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Mentions: Scirrhous type GC secretes a larger amount of active form TGF-β than non-scirrhous type GC does,(32) and TGF-β has an important pathological and biological role in scirrhous type GC.(5,7,33,34) To investigate the effect of TGF-β1 on miR-143 and collagen type III expression, NF-38 and CaF-38 were treated with TGF-β1, and their miR-143 expression levels were monitored by qRT-PCR. There were no differences in the expression of endogenous TGF-β1, TGF-β2, or TGF-β3 between NF-38 and CaF-38 (Fig. S2). Treatment with TGF-β1 resulted in strong induction of miR-143 and collagen type III mRNA expression within 96 h in both fibroblasts (Fig. 4a). However, the induction of collagen type III mRNA in fibroblasts by TGF-β1 was significantly suppressed by pretreatment with miR-143 inhibitor (Fig. 4b,c). Interestingly, miR-143 inhibitor significantly suppressed the expression of p-SMAD2 (Fig. 4d), and SMAD4 siRNA significantly downregulated miR-143 and collagen type III mRNA expression in each fibroblast (Fig. 4e). These data imply that miR-143 is deeply involved in the regulation of collagen type III expression by TGF-β/SMAD signaling in NF and CaF.
Affiliation: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.