MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer.
MicroRNA-143 regulates collagen type III expression in stromal fibroblasts of scirrhous type gastric cancer.
复制标题
DOI：
10.1111/cas.12329
复制
发表时间：
2014-02
期刊：
影响因子：
5.7
通讯作者：
Yasui W
中科院分区：
文献类型：
--
作者：
Naito Y;Sakamoto N;Oue N;Yashiro M;Sentani K;Yanagihara K;Hirakawa K;Yasui W
胃癌（GC）是全世界最常见的恶性肿瘤之一。尤其是硬质型GC具有高度转移性，临床特点是疾病进展快、预后差。 MicroRNA (miRNA) 在癌症的发生和进展中发挥着至关重要的作用。在本研究中，我们通过 miRNA 微阵列分析鉴定了几种在硬质型 GC 中表达水平高于非硬质型 GC 的 miRNA。其中，硬质型GC中的microRNA-143（miR-143）表达高于非硬质型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，但癌细胞不表达。在基质细胞中，miR-143 通过激活转化生长因子-β)/SMAD 信号传导增强正常胃成纤维细胞和癌症相关成纤维细胞中 III 型胶原蛋白的表达。此外，GC 中 miR-143 的高表达与癌症特异性死亡率较差相关（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'-deoxycytidine 处理 GC 细胞系可恢复 miR-143 的表达，而前体 miR-143 会抑制癌细胞侵袭。这些数据表明，miR-143通过诱导基质成纤维细胞中的胶原表达来调节硬质型GC的纤维化，并且miR-143表达可作为GC的预后标志物。
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.
登录
查看更多内容
影响因子：
4.8
作者：
Long, Xiaochun;Miano, Joseph M.
通讯作者：
Miano, Joseph M.
DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
影响因子：
20.1
作者：
Kim, Hyo Jung;Kim, Min Young;Seo, Han Geuk
通讯作者：
Seo, Han Geuk
影响因子：
14.8
作者：
Nuovo, Gerard J.;Elton, Terry S.;Nana-Sinkam, Patrick;Volinia, Stefano;Croce, Carlo M.;Schmittgen, Thomas D.
通讯作者：
Schmittgen, Thomas D.
影响因子：
5.7
作者：
Fuyuhiro, Yuhiko;Yashiro, Masakazu;Hirakawa, Kosei
通讯作者：
Hirakawa, Kosei