MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer
MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer
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DOI：
10.3892/or.2014.3333
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发表时间：
2014-10-01
期刊：
影响因子：
4.2
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
--
作者：
Naito, Yutaka;Yasuno, Kyohei;Yasui, Wataru
胃癌是世界范围内最常见的恶性肿瘤之一。尤其是硬癌型胃癌转移性强，临床上表现为病情进展快，预后差。microRNAs（miRNAs）在癌症的发生和发展中起着至关重要的作用。我们先前通过微阵列分析证明microRNA-145（miR-145）是硬结型GC与非硬结型GC中更高表达的miRNA之一。在本研究中，我们研究了miR-145在硬化型胃癌中的作用。定量RT-PCR检测结果显示，硬化型胃癌组织中miR-145的表达水平高于非硬化型胃癌及相应的正常组织。与miR-145低表达的患者相比，miR-145高表达的GC患者处于更晚期的肿瘤阶段（P=0.0156），并且具有更多的硬化型组织学类型（P=0.0054）。此外，miR-145表达与胃癌患者的不良预后显著相关（P=0.0438）。miR-145的表达定位于硬化型胃癌的间质成纤维细胞，而不是癌细胞。miR-145通过转化生长因子-β的处理诱导，并且它增强了正常胃成纤维细胞和癌症相关成纤维细胞中肌成纤维细胞的标志物α-平滑肌肌动蛋白的表达。这些数据表明，miR-145可能通过调节肿瘤周围成纤维细胞的活化而促进硬化型GC的进展。
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. We previously demonstrated by microarray analysis that microRNA-145 (miR-145) is one of the more highly expressed miRNAs in scirrhous type GC vs. non-scirrhous types of GC. In the present study, we investigated the role of miR-145 in scirrhous type GC. The expression levels of miR-145 assessed by quantitative RT-PCR were higher in scirrhous type GC tissue samples than in non-scirrhous type GC and corresponding normal tissues. GC patients with high miR-145 expression were at a more advanced tumor stage (P=0.0156) and had more scirrhous type histology (P=0.0054) than those with low miR-145 expression. Furthermore, miR-145 expression was significantly associated with poor prognosis in GC patients (P=0.0438). miR-145 expression was localized in stromal fibroblasts of scirrhous type GC but not in cancer cells. miR-145 was induced by treatment by transforming growth factor-beta, and it enhanced the expression of a-smooth muscle actin, a marker of myofibroblasts, in both normal gastric fibroblasts and cancer-associated fibroblasts. These data suggest that miR-145 may contribute to the progression of scirrhous type GC by regulating activation of peri-tumoral fibroblasts.