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: Because miR-143 was found to be expressed in stromal fibroblasts but not in cancer cells, we sought to investigate the function of miR-143 in stromal fibroblasts. Scirrhous type GC produces abundant collagen and thus promotes fibrosis.(31,32) We previously reported that collagen type III expression is associated with scirrhous type GC.(6,7) We first examined collagen type III expression in scirrhous type GC tissue by immunostaining and, as expected, collagen type III was detected in fibrillar bundles of scirrhous type GC (Fig. 3a). Collagen type III mRNA expression was examined in GC and fibroblasts by qRT-PCR. High levels of collagen type III mRNA expression were observed in stromal fibroblasts that retained high miR-143 expression (Fig. 3b). To assess the relation between collagen type III and miR-143, NF-38 and CaF-38 were selected because they had the highest miR-143 and collagen type III mRNA expression (Fig. 3b). Transfection of miR-143 inhibitor significantly suppressed collagen type III expression (Fig. 3c–e). In contrast, transfection of miR-143 precursor sustained or increased collagen type III expression (Fig. 3c–e). These data suggest that miR-143 positively regulates collagen type III expression in stromal fibroblasts of scirrhous type GC.
Affiliation: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.