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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. Micro RNA s (mi RNA s) play crucial roles in cancer development and progression. In the present study, we identified several mi RNA s that are expressed at higher levels in scirrhous type  GC  than in non‐scirrhous type  GC  by mi RNA  microarray analysis. Among these, micro RNA ‐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 .

Micro RNA ‐143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer