Abstract 4197: Function of microRNA-143 and its potential of prognostic factor in scirrhous type gastric cancer.

Abstract

Abstract Gastric cancer (GC) is one of the most common malignancies worldwide. Scirrhous type GC is highly metastatic and characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs), small non-coding RNA of 19-25 nucleotides, play a part in crucial biological processes and also have an important role in cancer development and progression. In the present study, we show that microRNA-143 (miR-143) is expressed at higher level in diffuse type GC than in intestinal type GC by microRNA microarray analysis. We investigated whether miR-143 is useful as a diagnostic marker of scirrhous type GC. Quantitative RT-PCR analysis revealed that miR-143 expression was low in GC in comparison with adjacent non-tumorous mucosa. Expression levels of miR-143 were higher in scirrhous type GC than those in other types of GC. Treatment of 5-aza-2′-deoxycytidine retrieved miR-143 expression, suggesting that miR-143 might be repressed by DNA methylation. Quantitative RT-PCR and in situ hybridization analysis showed that miR-143 is expressed at higher level in normal fibroblast and cancer associated fibroblast cell lines than in GC cell lines, indicating that major source of miR-143 in cancer tissue is stromal fibroblasts rather than cancer cells. miR-143 knock down by RNAi repressed collagen type III expression in normal fibroblast and cancer associated fibroblast cell lines. Furthermore, TGF-β treatment induced expression of miR-143 and collagen type III mRNA, and this induction of collagen type III mRNA was repressed by miR-143 knock down. We also studied the relation of miR-143 expression with GC patient prognosis (n=68). High miR-143 expression was associated with worse prognosis (P=0.0141). These data suggest that miR-143 regulates fibrosis of scirrhous type GC through induction of collagen expression in stromal fibroblasts and miR-143 expression is a prognostic marker of GC. Citation Format: Yutaka Naito, Naoya Sakamoto, Naohiro Uraoka, Kazuhiro Sentani, Naohide Oue, Masakazu Yashiro, Kosei Hirakawa, Wataru Yasui. Function of microRNA-143 and its potential of prognostic factor in scirrhous type gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4197. doi:10.1158/1538-7445.AM2013-4197