MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer.

スキルス胃癌の間質の線維芽細胞においてMicroRNA-143はcollagen type IIIの発現を制御する

Naito Yutaka

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 cancerassociated 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.

Collagen type III

fibroblast

gastric cancer

microRNA-143

transforming growth factor-β

Medical sciences [ 490 ]

eng

Copyright(c) by Author

[Created] 2014-11-21

Yutaka Naito, Naoya Sakamoto, Naohide Oue, Masakazu Yashiro, Kazuhiro Sentani, Kazuyoshi Yanagihara, Kosei Hirakawa and Wataru Yasui; MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer; Cancer Science Volume 105, Issue 2, pages 228-235, February 2014 (DOI: 10.1111/cas.12329) references

[DOI] http://dx.doi.org/10.1111/cas.12329 references

広島大学