Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Cancer Sci. 2014 Feb;105(2):228-35. doi: 10.1111/cas.12329. Epub 2014 Jan 8.
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 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.
胃癌（GC）是全球最常见的恶性肿瘤之一。特别是硬癌型 GC 具有高度转移性，临床上表现为疾病快速进展和预后不良。MicroRNAs（miRNAs）在癌症的发生和发展中起着至关重要的作用。在本研究中，我们通过 miRNA 微阵列分析鉴定出几种在硬癌型 GC 中表达水平高于非硬癌型 GC 的 miRNAs。其中，miR-143 在硬癌型 GC 中的表达高于非硬癌型 GC。原位杂交和定量 RT-PCR 分析表明，miR-143 由基质成纤维细胞表达，但不由癌细胞表达。在基质细胞中，miR-143 通过激活转化生长因子-β）/SMAD 信号通路增强正常胃成纤维细胞和癌相关成纤维细胞中胶原 III 型的表达。此外，GC 中高 miR-143 表达与更差的癌症特异性死亡率相关（P=0.0141）。多变量分析显示，miR-143 是一个独立的预后因素。用 5-aza-2'-脱氧胞苷处理 GC 细胞系可恢复 miR-143 的表达，而前体 miR-143 可抑制癌细胞侵袭。这些数据表明，miR-143 通过诱导基质成纤维细胞中胶原的表达来调节硬癌型 GC 的纤维化，并且 miR-143 的表达可作为 GC 的预后标志物。
Zotero 插件
