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: To elucidate why scirrhous-type GC possesses high miR-143 expression, we first investigated the localization of miR-143 expression in scirrhous type GC tissue by in situ hybridization of miR-143 in combination with immunostaining using markers for epithelial cells (CAM5.2), stromal fibroblasts (vimentin), and CaFs (α-SMA; Fig. 2a–c, Fig. S1).(30) Cancer fibroblasts, also termed myofibroblasts or activated fibroblasts, are well known as a major component of cancer stroma and play an important role in the regulation of cancer cell proliferation and metastasis.(5,30) In cancerous regions, double staining revealed that expression of miR-143 was observed in α-SMA- or vimentin-positive fibroblastic cells (Fig. 2a,b) but was not colocalized with CAM5.2-positive cancer cells (Fig. 2c). However, in non-neoplastic regions, miR-143 was highly expressed in normal epithelial cells, but the expression was faint or not present in stromal fibroblasts in non-neoplastic tissue (data not shown). Expression of miR-143 was also examined in 9 GC cell lines, as well as in NFs and CaFs. Expression of miR-143 was evident in NFs and CaFs, but was undetectable in GC cell lines (Fig. 2d). Moreover, the expression levels of miR-143 were higher in CaFs than in NFs, and CaFs derived from scirrhous type GC showed a tendency toward higher expression of miR-143 (Fig. 2d). These data indicated that miR-143 is localized to epithelial cells in normal gastric tissue, but its localization is changed to surrounding stromal fibroblasts, but not cancer cells, in scirrhous type GC.
Affiliation: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.